347 results on '"Gibbs, J Raphael"'
Search Results
2. Profiling complex repeat expansions in RFC1 in Parkinson’s disease
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Alvarez Jerez, Pilar, Daida, Kensuke, Miano-Burkhardt, Abigail, Iwaki, Hirotaka, Malik, Laksh, Cogan, Guillaume, Makarious, Mary B., Sullivan, Roisin, Vandrovcova, Jana, Ding, Jinhui, Gibbs, J. Raphael, Markham, Androo, Nalls, Mike A., Kesharwani, Rupesh K., Sedlazeck, Fritz J., Casey, Bradford, Hardy, John, Houlden, Henry, Blauwendraat, Cornelis, Singleton, Andrew B., and Billingsley, Kimberley J.
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- 2024
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3. Genetic analysis of the X chromosome in people with Lewy body dementia nominates new risk loci
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Bayram, Ece, Reho, Paolo, Litvan, Irene, Ding, Jinhui, Gibbs, J. Raphael, Dalgard, Clifton L., Traynor, Bryan J., Scholz, Sonja W., and Chia, Ruth
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- 2024
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4. Genome-wide structural variant analysis identifies risk loci for non-Alzheimer’s dementias
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Soltis, Anthony R., Viollet, Coralie, Sukumar, Gauthaman, Alba, Camille, Lott, Nathaniel, McGrath Martinez, Elisa, Tuck, Meila, Singh, Jatinder, Bacikova, Dagmar, Zhang, Xijun, Hupalo, Daniel N., Adeleye, Adelani, Wilkerson, Matthew D., Pollard, Harvey B., Dalgard, Clifton L., Black, Sandra E., Gan-Or, Ziv, Keith, Julia, Masellis, Mario, Rogaeva, Ekaterina, Brice, Alexis, Lesage, Suzanne, Xiromerisiou, Georgia, Calvo, Andrea, Canosa, Antonio, Chio, Adriano, Logroscino, Giancarlo, Mora, Gabriele, Krüger, Reijko, May, Patrick, Alcolea, Daniel, Clarimon, Jordi, Fortea, Juan, Gonzalez-Aramburu, Isabel, Infante, Jon, Lage, Carmen, Lleó, Alberto, Pastor, Pau, Sanchez-Juan, Pascual, Brett, Francesca, Aarsland, Dag, Al-Sarraj, Safa, Attems, Johannes, Gentleman, Steve, Hardy, John A., Hodges, Angela K., Love, Seth, McKeith, Ian G., Morris, Christopher M., Morris, Huw R., Palmer, Laura, Pickering-Brown, Stuart, Ryten, Mina, Thomas, Alan J., Troakes, Claire, Albert, Marilyn S., Barrett, Matthew J., Beach, Thomas G., Bekris, Lynn M., Bennett, David A., Boeve, Bradley F., Dawson, Ted M., Dickson, Dennis W., Faber, Kelley, Ferman, Tanis, Ferrucci, Luigi, Flanagan, Margaret E., Foroud, Tatiana M., Ghetti, Bernardino, Gibbs, J. Raphael, Goate, Alison, Goldstein, David S., Graff-Radford, Neill R., Kaufmann, Horacio, Kukull, Walter A., Leverenz, James B., Lopez, Grisel, Mao, Qinwen, Masliah, Eliezer, Monuki, Edwin, Newell, Kathy L., Palma, Jose-Alberto, Perkins, Matthew, Pletnikova, Olga, Renton, Alan E., Resnick, Susan M., Rosenthal, Liana S., Ross, Owen A., Scherzer, Clemens R., Serrano, Geidy E., Shakkottai, Vikram G., Sidransky, Ellen, Tanaka, Toshiko, Tayebi, Nahid, Topol, Eric, Torkamani, Ali, Troncoso, Juan C., Woltjer, Randy, Wszolek, Zbigniew K., Scholz, Sonja W., Baloh, Robert H., Bowser, Robert, Broach, James, Camu, William, Chiò, Adriano, Cooper-Knock, John, Drepper, Carsten, Drory, Vivian E., Dunckley, Travis L., Feldman, Eva, Fratta, Pietro, Gerhard, Glenn, Gibson, Summer B., Glass, Jonathan D., Harms, Matthew B., Heiman-Patterson, Terry D., Jansson, Lilja, Kirby, Janine, Kwan, Justin, Laaksovirta, Hannu, Landers, John E., Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, MacGowan, Daniel J.L., Maragakis, Nicholas J., Mouzat, Kevin, Myllykangas, Liisa, Orrell, Richard W., Ostrow, Lyle W., Pamphlett, Roger, Pioro, Erik, Pulst, Stefan M., Ravits, John M., Robberecht, Wim, Rothstein, Jeffrey D., Sendtner, Michael, Shaw, Pamela J., Sidle, Katie C., Simmons, Zachary, Stein, Thor, Stone, David J., Tienari, Pentti J., Traynor, Bryan J., Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M., Van Den Bosch, Ludo, Zinman, Lorne, Kaivola, Karri, Chia, Ruth, Ding, Jinhui, Rasheed, Memoona, Fujita, Masashi, Menon, Vilas, Walton, Ronald L., Collins, Ryan L., Billingsley, Kimberley, Brand, Harrison, Talkowski, Michael, Zhao, Xuefang, Dewan, Ramita, Stark, Ali, Ray, Anindita, Solaiman, Sultana, Alvarez Jerez, Pilar, Malik, Laksh, Tienari, Pentti, Mazzini, Letizia, D'Alfonso, Sandra, Moglia, Cristina, and De Jager, Philip L.
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- 2023
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5. Genetic determinants of survival in progressive supranuclear palsy: a genome-wide association study
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Mok, Kin Y., Murphy, David P., Al-Sarraj, Safa, Troakes, Claire, Gentleman, Steve M., Allinson, Kieren S.J., Jaunmuktane, Zane, Holton, Janice L., Lees, Andrew J., Morris, Christopher M., Compta, Yaroslau, Gelpi, Ellen, van Swieten, John C., Rajput, Alex, Ferguson, Leslie, Cookson, Mark R., Gibbs, J. Raphael, Blauwendraat, Cornelis, Ding, Jinhui, Chia, Ruth, Traynor, Bryan J., Pantelyat, Alexander, Viollet, Coralie, Pletnikova, Olga, Troncoso, Juan C., Rosenthal, Liana S., Boxer, Adam L., Respondek, Gesine, Arzberger, Thomas, Roeber, Sigrun, Giese, Armin, Burn, David J., Pavese, Nicola, Gerhard, Alexander, Kobylecki, Christopher, Leigh, P. Nigel, Church, Alistair, T.M. Hu, Michele, Jabbari, Edwin, Koga, Shunsuke, Valentino, Rebecca R, Reynolds, Regina H, Ferrari, Raffaele, Tan, Manuela M X, Rowe, James B, Dalgard, Clifton L, Scholz, Sonja W, Dickson, Dennis W, Warner, Thomas T, Revesz, Tamas, Höglinger, Günter U, Ross, Owen A, Ryten, Mina, Hardy, John, Shoai, Maryam, and Morris, Huw R
- Published
- 2021
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6. Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture
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Chia, Ruth, Sabir, Marya S., Bandres-Ciga, Sara, Saez-Atienzar, Sara, Reynolds, Regina H., Gustavsson, Emil, Walton, Ronald L., Ahmed, Sarah, Viollet, Coralie, Ding, Jinhui, Makarious, Mary B., Diez-Fairen, Monica, Portley, Makayla K., Shah, Zalak, Abramzon, Yevgeniya, Hernandez, Dena G., Blauwendraat, Cornelis, Stone, David J., Eicher, John, Parkkinen, Laura, Ansorge, Olaf, Clark, Lorraine, Honig, Lawrence S., Marder, Karen, Lemstra, Afina, St George-Hyslop, Peter, Londos, Elisabet, Morgan, Kevin, Lashley, Tammaryn, Warner, Thomas T., Jaunmuktane, Zane, Galasko, Douglas, Santana, Isabel, Tienari, Pentti J., Myllykangas, Liisa, Oinas, Minna, Cairns, Nigel J., Morris, John C., Halliday, Glenda M., Van Deerlin, Vivianna M., Trojanowski, John Q., Grassano, Maurizio, Calvo, Andrea, Mora, Gabriele, Canosa, Antonio, Floris, Gianluca, Bohannan, Ryan C., Brett, Francesca, Gan-Or, Ziv, Geiger, Joshua T., Moore, Anni, May, Patrick, Krüger, Rejko, Goldstein, David S., Lopez, Grisel, Tayebi, Nahid, Sidransky, Ellen, Norcliffe-Kaufmann, Lucy, Palma, Jose-Alberto, Kaufmann, Horacio, Shakkottai, Vikram G., Perkins, Matthew, Newell, Kathy L., Gasser, Thomas, Schulte, Claudia, Landi, Francesco, Salvi, Erika, Cusi, Daniele, Masliah, Eliezer, Kim, Ronald C., Caraway, Chad A., Monuki, Edwin S., Brunetti, Maura, Dawson, Ted M., Rosenthal, Liana S., Albert, Marilyn S., Pletnikova, Olga, Troncoso, Juan C., Flanagan, Margaret E., Mao, Qinwen, Bigio, Eileen H., Rodríguez-Rodríguez, Eloy, Infante, Jon, Lage, Carmen, González-Aramburu, Isabel, Sanchez-Juan, Pascual, Ghetti, Bernardino, Keith, Julia, Black, Sandra E., Masellis, Mario, Rogaeva, Ekaterina, Duyckaerts, Charles, Brice, Alexis, Lesage, Suzanne, Xiromerisiou, Georgia, Barrett, Matthew J., Tilley, Bension S., Gentleman, Steve, Logroscino, Giancarlo, Serrano, Geidy E., Beach, Thomas G., McKeith, Ian G., Thomas, Alan J., Attems, Johannes, Morris, Christopher M., Palmer, Laura, Love, Seth, Troakes, Claire, Al-Sarraj, Safa, Hodges, Angela K., Aarsland, Dag, Klein, Gregory, Kaiser, Scott M., Woltjer, Randy, Pastor, Pau, Bekris, Lynn M., Leverenz, James B., Besser, Lilah M., Kuzma, Amanda, Renton, Alan E., Goate, Alison, Bennett, David A., Scherzer, Clemens R., Morris, Huw R., Ferrari, Raffaele, Albani, Diego, Pickering-Brown, Stuart, Faber, Kelley, Kukull, Walter A., Morenas-Rodriguez, Estrella, Lleó, Alberto, Fortea, Juan, Alcolea, Daniel, Clarimon, Jordi, Nalls, Mike A., Ferrucci, Luigi, Resnick, Susan M., Tanaka, Toshiko, Foroud, Tatiana M., Graff-Radford, Neill R., Wszolek, Zbigniew K., Ferman, Tanis, Boeve, Bradley F., Hardy, John A., Topol, Eric J., Torkamani, Ali, Singleton, Andrew B., Ryten, Mina, Dickson, Dennis W., Chiò, Adriano, Ross, Owen A., Gibbs, J. Raphael, Dalgard, Clifton L., Traynor, Bryan J., and Scholz, Sonja W.
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- 2021
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7. Exploring dementia and neuronal ceroid lipofuscinosis genes in 100 FTD-like patients from 6 towns and rural villages on the Adriatic Sea cost of Apulia
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Sassi, Celeste, Capozzo, Rosa, Hammer, Monia, Zecca, Chiara, Federoff, Monica, Blauwendraat, Cornelis, Bernstein, Nick, Ding, Jinhui, Gibbs, J. Raphael, Price, Timothy, Singleton, Andrew, and Logroscino, Giancarlo
- Published
- 2021
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8. Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies
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Adarmes-Gómez, Astrid D, Aguilar, Miquel, Aitkulova, Akbota, Akhmetzhanov, Vadim, Alcalay, Roy N, Alvarez, Ignacio, Alvarez, Victoria, Bandres-Ciga, Sara, Barrero, Francisco Javier, Bergareche Yarza, Jesús Alberto, Bernal-Bernal, Inmaculada, Billingsley, Kimberley, Blauwendraat, Cornelis, Blazquez, Marta, Bonilla-Toribio, Marta, Botía, Juan A, Boungiorno, María Teresa, Bras, Jose, Brice, Alexis, Brockmann, Kathrin, Bubb, Vivien, Buiza-Rueda, Dolores, Cámara, Ana, Carrillo, Fátima, Carrión-Claro, Mario, Cerdan, Debora, Chelban, Viorica, Clarimón, Jordi, Clarke, Carl, Compta, Yaroslau, Cookson, Mark R, Corvol, Jean-Christophe, Craig, David W, Danjou, Fabrice, Diez-Fairen, Monica, Dols-Icardo, Oriol, Duarte, Jacinto, Duran, Raquel, Escamilla-Sevilla, Francisco, Escott-Price, Valentina, Ezquerra, Mario, Faghri, Faraz, Feliz, Cici, Fernández, Manel, Fernández-Santiago, Rubén, Finkbeiner, Steven, Foltynie, Thomas, Gan-Or, Ziv, Garcia, Ciara, García-Ruiz, Pedro, Gasser, Thomas, Gibbs, J Raphael, Gomez Heredia, Maria Jose, Gómez-Garre, Pilar, González, Manuel Menéndez, Gonzalez-Aramburu, Isabel, Guelfi, Sebastian, Guerreiro, Rita, Hardy, John, Hassin-Baer, Sharon, Hernandez, Dena G, Heutink, Peter, Hoenicka, Janet, Holmans, Peter, Houlden, Henry, Infante, Jon, Iwaki, Hirotaka, Jesús, Silvia, Jimenez-Escrig, Adriano, Kaishybayeva, Gulnaz, Kaiyrzhanov, Rauan, Karimova, Altynay, Kia, Demis A, Kinghorn, Kerri J, Koks, Sulev, Krohn, Lynne, Kulisevsky, Jaime, Labrador-Espinosa, Miguel A, Leonard, Hampton L, Lesage, Suzanne, Lewis, Patrick, Lopez-Sendon, Jose Luis, Lovering, Ruth, Lubbe, Steven, Lungu, Codrin, Macias, Daniel, Majamaa, Kari, Manzoni, Claudia, Marín, Juan, Marinus, Johan, Marti, Maria Jose, Martinez, Maria, Martínez Torres, Irene, Martínez-Castrillo, Juan Carlos, Mata, Marina, Mencacci, Niccolo E, Méndez-del-Barrio, Carlota, Middlehurst, Ben, Mínguez, Adolfo, Mir, Pablo, Mok, Kin Y, Morris, Huw R, Muñoz, Esteban, Nalls, Mike A, Narendra, Derek, Noyce, Alastair J, Ojo, Oluwadamilola O, Okubadejo, Njideka U, Pagola, Ana Gorostidi, Pastor, Pau, Perez Errazquin, Francisco, Periñán-Tocino, Teresa, Pihlstrom, Lasse, Plun-Favreau, Helene, Quinn, John, R'Bibo, Lea, Reed, Xylena, Rezola, Elisabet Mondragon, Rizig, Mie, Rizzu, Patrizia, Robak, Laurie, Rodriguez, Antonio Sanchez, Rouleau, Guy A, Ruiz-Martínez, Javier, Ruz, Clara, Ryten, Mina, Sadykova, Dinara, Scholz, Sonja W, Schreglmann, Sebastian, Schulte, Claudia, Sharma, Manu, Shashkin, Chingiz, Shulman, Joshua M, Sierra, María, Siitonen, Ari, Simón-Sánchez, Javier, Singleton, Andrew B, Suarez-Sanmartin, Esther, Taba, Pille, Tabernero, Cesar, Tan, Manuela X, Tartari, Juan Pablo, Tejera-Parrado, Cristina, Toft, Mathias, Tolosa, Eduard, Trabzuni, Daniah, Valldeoriola, Francesc, van Hilten, Jacobus J, Van Keuren-Jensen, Kendall, Vargas-González, Laura, Vela, Lydia, Vives, Francisco, Williams, Nigel, Wood, Nicholas W, Zharkinbekova, Nazira, Zharmukhanov, Zharkyn, Zholdybayeva, Elena, Zimprich, Alexander, Ylikotila, Pauli, Shulman, Lisa M., von Coelln, Rainer, Reich, Stephen, Savitt, Joseph, Agee, Michelle, Alipanahi, Babak, Auton, Adam, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Fontanillas, Pierre, Furlotte, Nicholas A., Huber, Karen E., Hicks, Barry, Jewett, Ethan M., Jiang, Yunxuan, Kleinman, Aaron, Lin, Keng-Han, Litterman, Nadia K., McCreight, Jennifer C., McIntyre, Matthew H., McManus, Kimberly F., Mountain, Joanna L., Noblin, Elizabeth S., Northover, Carrie A.M., Pitts, Steven J., Poznik, G. David, Sathirapongsasuti, J. Fah, Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce, Vacic, Vladimir, Wang, Xin, Wilson, Catherine H., Anderson, Tim, Bentley, Steven, Dalrymple-Alford, John, Fowdar, Javed, Gratten, Jacob, Halliday, Glenda, Henders, Anjali K., Hickie, Ian, Kassam, Irfahan, Kennedy, Martin, Kwok, John, Lewis, Simon, Mellick, George, Montgomery, Grant, Pearson, John, Pitcher, Toni, Sidorenko, Julia, Silburn, Peter A., Vallerga, Costanza L., Visscher, Peter M., Wallace, Leanne, Wray, Naomi R., Xue, Angli, Yang, Jian, Zhang, Futao, Vallerga, Costanza L, Heilbron, Karl, Chang, Diana, Tan, Manuela, Young, Emily, Pihlstrøm, Lasse, Leonard, Hampton, Botia, Juan A, Jankovic, Joseph, Shulman, Lisa M, Sutherland, Margaret, Tienari, Pentti, Andreassen, Ole A, Bangale, Tushar, Hinds, David A, Hardy, John A, Visscher, Peter M, and Graham, Robert R
- Published
- 2019
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9. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
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Logullo, Francesco O., Simone, Isabella, Logroscino, Giancarlo, Salvi, Fabrizio, Bartolomei, Ilaria, Borghero, Giuseppe, Murru, Maria Rita, Costantino, Emanuela, Pani, Carla, Puddu, Roberta, Caredda, Carla, Piras, Valeria, Tranquilli, Stefania, Cuccu, Stefania, Corongiu, Daniela, Melis, Maurizio, Milia, Antonio, Marrosu, Francesco, Marrosu, Maria Giovanna, Floris, Gianluca, Cannas, Antonino, Capasso, Margherita, Caponnetto, Claudia, Mancardi, Gianluigi, Origone, Paola, Mandich, Paola, Conforti, Francesca L., Cavallaro, Sebastiano, Mora, Gabriele, Marinou, Kalliopi, Sideri, Riccardo, Penco, Silvana, Mosca, Lorena, Lunetta, Christian, Pinter, Giuseppe Lauria, Corbo, Massimo, Riva, Nilo, Carrera, Paola, Volanti, Paolo, Mandrioli, Jessica, Fini, Nicola, Fasano, Antonio, Tremolizzo, Lucio, Arosio, Alessandro, Ferrarese, Carlo, Trojsi, Francesca, Tedeschi, Gioacchino, Monsurrò, Maria Rosaria, Piccirillo, Giovanni, Femiano, Cinzia, Ticca, Anna, Ortu, Enzo, La Bella, Vincenzo, Spataro, Rossella, Colletti, Tiziana, Sabatelli, Mario, Zollino, Marcella, Conte, Amelia, Luigetti, Marco, Lattante, Serena, Marangi, Giuseppe, Santarelli, Marialuisa, Petrucci, Antonio, Pugliatti, Maura, Pirisi, Angelo, Parish, Leslie D., Occhineri, Patrizia, Giannini, Fabio, Battistini, Stefania, Ricci, Claudia, Benigni, Michele, Cau, Tea B., Loi, Daniela, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Barberis, Marco, Restagno, Gabriella, Casale, Federico, Marrali, Giuseppe, Fuda, Giuseppe, Ossola, Irene, Cammarosano, Stefania, Canosa, Antonio, Ilardi, Antonio, Manera, Umberto, Grassano, Maurizio, Tanel, Raffaella, Pisano, Fabrizio, Harms, Matthew B., Goldstein, David B., Shneider, Neil A., Goutman, Stephen, Simmons, Zachary, Miller, Timothy M., Chandran, Siddharthan, Pal, Suvankar, Manousakis, Georgios, Appel, Stanley H., Simpson, Ericka, Wang, Leo, Baloh, Robert H., Gibson, Summer, Bedlack, Richard, Lacomis, David, Sareen, Dhruv, Sherman, Alexander, Bruijn, Lucie, Penny, Michelle, Allen, Andrew S., Appel, Stanley, Bedlack, Richard S., Boone, Braden E., Brown, Robert, Carulli, John P., Chesi, Alessandra, Chung, Wendy K., Cirulli, Elizabeth T., Cooper, Gregory M., Couthouis, Julien, Day-Williams, Aaron G., Dion, Patrick A., Gitler, Aaron D., Glass, Jonathan D., Han, Yujun, Harris, Tim, Hayes, Sebastian D., Jones, Angela L., Keebler, Jonathan, Krueger, Brian J., Lasseigne, Brittany N., Levy, Shawn E., Lu, Yi-Fan, Maniatis, Tom, McKenna-Yasek, Diane, Myers, Richard M., Petrovski, Slavé, Pulst, Stefan M., Raphael, Alya R., Ravits, John M., Ren, Zhong, Rouleau, Guy A., Sapp, Peter C., Sims, Katherine B., Staropoli, John F., Waite, Lindsay L., Wang, Quanli, Wimbish, Jack R., Xin, Winnie W., Phatnani, Hemali, Kwan, Justin, Broach, James R., Arcila-Londono, Ximena, Lee, Edward B., Van Deerlin, Vivianna M., Fraenkel, Ernest, Ostrow, Lyle W., Baas, Frank, Zaitlen, Noah, Berry, James D., Malaspina, Andrea, Fratta, Pietro, Cox, Gregory A., Thompson, Leslie M., Finkbeiner, Steve, Dardiotis, Efthimios, Hornstein, Eran, MacGowan, Daniel J., Heiman-Patterson, Terry, Hammell, Molly G., Patsopoulos, Nikolaos A., Dubnau, Joshua, Nath, Avindra, Kaye, Julia, Finkbeiner, Steven, Wyman, Stacia, LeNail, Alexander, Lima, Leandro, Rothstein, Jeffrey D., Svendsen, Clive N., Van Eyk, Jenny, Maragakis, Nicholas J., Kolb, Stephen J., Cudkowicz, Merit, Baxi, Emily, Benatar, Michael, Taylor, J. Paul, Wu, Gang, Rampersaud, Evadnie, Wuu, Joanne, Rademakers, Rosa, Züchner, Stephan, Schule, Rebecca, McCauley, Jacob, Hussain, Sumaira, Cooley, Anne, Wallace, Marielle, Clayman, Christine, Barohn, Richard, Statland, Jeffrey, Ravits, John, Swenson, Andrea, Jackson, Carlayne, Trivedi, Jaya, Khan, Shaida, Katz, Jonathan, Jenkins, Liberty, Burns, Ted, Gwathmey, Kelly, Caress, James, McMillan, Corey, Elman, Lauren, Pioro, Erik, Heckmann, Jeannine, So, Yuen, Walk, David, Maiser, Samuel, Zhang, Jinghui, Silani, Vincenzo, Ticozzi, Nicola, Gellera, Cinzia, Ratti, Antonia, Taroni, Franco, Lauria, Giuseppe, Verde, Federico, Fogh, Isabella, Tiloca, Cinzia, Comi, Giacomo P., Sorarù, Gianni, Cereda, Cristina, D’Alfonso, Sandra, Corrado, Lucia, De Marchi, Fabiola, Corti, Stefania, Ceroni, Mauro, Mazzini, Letizia, Siciliano, Gabriele, Filosto, Massimiliano, Inghilleri, Maurizio, Peverelli, Silvia, Colombrita, Claudia, Poletti, Barbara, Maderna, Luca, Del Bo, Roberto, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, Pensato, Viviana, Castellotti, Barbara, Camu, William, Mouzat, Kevin, Lumbroso, Serge, Corcia, Philippe, Meininger, Vincent, Besson, Gérard, Lagrange, Emmeline, Clavelou, Pierre, Guy, Nathalie, Couratier, Philippe, Vourch, Patrick, Danel, Véronique, Bernard, Emilien, Lemasson, Gwendal, Al Kheifat, Ahmad, Al-Chalabi, Ammar, Andersen, Peter, Basak, A. Nazli, Blair, Ian P., Chio, Adriano, Cooper-Knock, Jonathan, de Carvalho, Mamede, Dekker, Annelot, Drory, Vivian, Redondo, Alberto Garcia, Gotkine, Marc, Hardiman, Orla, Hide, Winston, Iacoangeli, Alfredo, Glass, Jonathan, Kenna, Kevin, Kiernan, Matthew, Kooyman, Maarten, Landers, John, McLaughlin, Russell, Middelkoop, Bas, Mill, Jonathan, Neto, Miguel Mitne, Moisse, Mattieu, Pardina, Jesus Mora, Morrison, Karen, Newhouse, Stephen, Pinto, Susana, Pulit, Sara, Robberecht, Wim, Shatunov, Aleksey, Shaw, Pamela, Shaw, Chris, Sproviero, William, Tazelaar, Gijs, van Damme, Philip, van den Berg, Leonard, van der Spek, Rick, van Eijk, Kristel, van Es, Michael, van Rheenen, Wouter, van Vugt, Joke, Veldink, Jan, Weber, Markus, Williams, Kelly L., Zatz, Mayana, Bauer, Denis C., Twine, Natalie A., Nicolas, Aude, Kenna, Kevin P., Renton, Alan E., Faghri, Faraz, Chia, Ruth, Dominov, Janice A., Kenna, Brendan J., Nalls, Mike A., Keagle, Pamela, Rivera, Alberto M., Murphy, Natalie A., van Vugt, Joke J.F.A., Geiger, Joshua T., Van der Spek, Rick A., Pliner, Hannah A., Shankaracharya, Smith, Bradley N., Topp, Simon D., Abramzon, Yevgeniya, Gkazi, Athina Soragia, Eicher, John D., Kenna, Aoife, Messina, Sonia, Simone, Isabella L., Ferrucci, Luigi, Moreno, Cristiane de Araujo Martins, Kamalakaran, Sitharthan, Musunuri, Rajeeva Lochan, Evani, Uday Shankar, Abhyankar, Avinash, Zody, Michael C., Wyman, Stacia K., LeNail, Alex, Van Eyk, Jennifer E., Laaksovirta, Hannu, Myllykangas, Liisa, Jansson, Lilja, Valori, Miko, Ealing, John, Hamdalla, Hisham, Rollinson, Sara, Pickering-Brown, Stuart, Orrell, Richard W., Sidle, Katie C., Hardy, John, Singleton, Andrew B., Johnson, Janel O., Arepalli, Sampath, Polak, Meraida, Asress, Seneshaw, Al-Sarraj, Safa, King, Andrew, Troakes, Claire, Vance, Caroline, de Belleroche, Jacqueline, ten Asbroek, Anneloor L.M.A., Muñoz-Blanco, José Luis, Hernandez, Dena G., Ding, Jinhui, Gibbs, J. Raphael, Scholz, Sonja W., Floeter, Mary Kay, Campbell, Roy H., Landi, Francesco, Bowser, Robert, MacGowan, Daniel J.L., Kirby, Janine, Pioro, Erik P., Pamphlett, Roger, Broach, James, Gerhard, Glenn, Dunckley, Travis L., Brady, Christopher B., Kowall, Neil W., Troncoso, Juan C., Le Ber, Isabelle, Heiman-Patterson, Terry D., Kamel, Freya, Van Den Bosch, Ludo, Strom, Tim M., Meitinger, Thomas, Van Eijk, Kristel R., Moisse, Matthieu, McLaughlin, Russell L., Van Es, Michael A., Boylan, Kevin B., Van Blitterswijk, Marka, Morrison, Karen E., Mora, Jesús S., Drory, Vivian E., Shaw, Pamela J., Turner, Martin R., Talbot, Kevin, Fifita, Jennifer A., Nicholson, Garth A., Esteban-Pérez, Jesús, García-Redondo, Alberto, Rogaeva, Ekaterina, Zinman, Lorne, Cooper-Knock, Johnathan, Brice, Alexis, Goutman, Stephen A., Feldman, Eva L., Gibson, Summer B., Van Damme, Philip, Ludolph, Albert C., Andersen, Peter M., Weishaupt, Jochen H., Trojanowski, John Q., Brown, Robert H., Jr., van den Berg, Leonard H., Veldink, Jan H., Stone, David J., Tienari, Pentti, Chiò, Adriano, Shaw, Christopher E., Traynor, Bryan J., and Landers, John E.
- Published
- 2018
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10. Clinical and genetic analyses of familial and sporadic frontotemporal dementia patients in Southern Italy
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Capozzo, Rosa, Sassi, Celeste, Hammer, Monia B., Arcuti, Simona, Zecca, Chiara, Barulli, Maria R., Tortelli, Rosanna, Gibbs, J. Raphael, Crews, Cynthia, Seripa, Davide, Carnicella, Francesco, Dell'Aquila, Claudia, Rossi, Marco, Tamma, Filippo, Valluzzi, Francesco, Brancasi, Bruno, Panza, Francesco, Singleton, Andrew B., and Logroscino, Giancarlo
- Published
- 2017
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11. Long‐Read Sequencing Resolves a Complex Structural Variant in PRKN Parkinson's Disease.
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Daida, Kensuke, Funayama, Manabu, Billingsley, Kimberley J., Malik, Laksh, Miano‐Burkhardt, Abigail, Leonard, Hampton L., Makarious, Mary B., Iwaki, Hirotaka, Ding, Jinhui, Gibbs, J. Raphael, Ishiguro, Mayu, Yoshino, Hiroyo, Ogaki, Kotaro, Oyama, Genko, Nishioka, Kenya, Nonaka, Risa, Akamatsu, Wado, Blauwendraat, Cornelis, and Hattori, Nobutaka
- Abstract
Background: Parkin RBR E3 ubiquitin‐protein ligase (PRKN) mutations are the most common cause of young onset and autosomal recessive Parkinson's disease (PD). PRKN is located in FRA6E, which is one of the common fragile sites in the human genome, making this region prone to structural variants. However, complex structural variants such as inversions of PRKN are seldom reported, suggesting that there are potentially unrevealed complex pathogenic PRKN structural variants. Objectives: To identify complex structural variants in PRKN using long‐read sequencing. Methods: We investigated the genetic cause of monozygotic twins presenting with a young onset dystonia‐parkinsonism using targeted sequencing, whole exome sequencing, multiple ligation probe amplification, and long‐read sequencing. We assessed the presence and frequency of complex inversions overlapping PRKN using whole‐genome sequencing data of Accelerating Medicines Partnership Parkinson's disease (AMP‐PD) and United Kingdom (UK)‐Biobank datasets. Results: Multiple ligation probe amplification identified a heterozygous exon three deletion in PRKN and long‐read sequencing identified a large novel inversion spanning over 7 Mb, including a large part of the coding DNA sequence of PRKN. We could diagnose the affected subjects as compound heterozygous carriers of PRKN. We analyzed whole genome sequencing data of 43,538 participants of the UK‐Biobank and 4941 participants of the AMP‐PD datasets. Nine inversions in the UK‐Biobank and two in AMP PD were identified and were considered potentially damaging and likely to affect PRKN expression. Conclusions: This is the first report describing a large 7 Mb inversion involving breakpoints outside of PRKN. This study highlights the importance of using long‐read sequencing for structural variant analysis in unresolved young‐onset PD cases. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA. [ABSTRACT FROM AUTHOR]
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- 2023
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12. Replication assessment of NUS1 variants in Parkinson's disease
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Bustos, Bernabe I., Bandres-Ciga, Sara, Gibbs, J. Raphael, Krainc, Dimitri, Mencacci, Niccolo E., Gan-Or, Ziv, and Lubbe, Steven J.
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- 2021
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13. Mitochondria function associated genes contribute to Parkinson’s Disease risk and later age at onset
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Billingsley, Kimberley J., Barbosa, Ines A., Bandrés-Ciga, Sara, Quinn, John P., Bubb, Vivien J., Deshpande, Charu, Botia, Juan A., Reynolds, Regina H., Zhang, David, Simpson, Michael A., Blauwendraat, Cornelis, Gan-Or, Ziv, Gibbs, J. Raphael, Nalls, Mike A., Singleton, Andrew, International Parkinson’s Disease Genomics Consortium (IPDGC), Ryten, Mina, and Koks, Sulev
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- 2019
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14. Genome-Wide Analysis of Structural Variants in Parkinson Disease
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Billingsley, Kimberley J, Ding, Jinhui, Hernandez, Dena, Torkamani, Ali, Ryten, Mina, Hardy, John, Consortium, UK Brain Expression, Chia, Ruth, Scholz, Sonja W, Traynor, Bryan J, Dalgard, Clifton L, Ehrlich, Debra J, Jerez, Pilar Alvarez, Tanaka, Toshiko, Ferrucci, Luigi, Beach, Thomas G, Serrano, Geidy E, Quinn, John P, Bubb, Vivien J, Collins, Ryan L, Zhao, Xuefang, Walker, Mark, Pierce-Hoffman, Emma, Illarionova, Anastasia, Brand, Harrison, Talkowski, Michael E, Casey, Bradford, Cookson, Mark R, Markham, Androo, Nalls, Mike A, Mahmoud, Medhat, Sedlazeck, Fritz J, Blauwendraat, Cornelis, Gibbs, J Raphael, Levine, Kristin, Singleton, Andrew B, Grenn, Francis P, Makarious, Mary B, Moore, Anni, Vitale, Daniel, and Reed, Xylena
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Neurology ,Neurology (clinical) ,ddc:610 - Abstract
Identification of genetic risk factors for Parkinson disease (PD) has to date been primarily limited to the study of single nucleotide variants, which only represent a small fraction of the genetic variation in the human genome. Consequently, causal variants for most PD risk are not known. Here we focused on structural variants (SVs), which represent a major source of genetic variation in the human genome. We aimed to discover SVs associated with PD risk by performing the first large-scale characterization of SVs in PD.We leveraged a recently developed computational pipeline to detect and genotype SVs from 7,772 Illumina short-read whole genome sequencing samples. Using this set of SV variants, we performed a genome-wide association study using 2,585 cases and 2,779 controls and identified SVs associated with PD risk. Furthermore, to validate the presence of these variants, we generated a subset of matched whole-genome long-read sequencing data.We genotyped and tested 3,154 common SVs, representing over 412 million nucleotides of previously uncatalogued genetic variation. Using long-read sequencing data, we validated the presence of three novel deletion SVs that are associated with risk of PD from our initial association analysis, including a 2 kb intronic deletion within the gene LRRN4.We identified three SVs associated with genetic risk of PD. This study represents the most comprehensive assessment of the contribution of SVs to the genetic risk of PD to date. ANN NEUROL 2023.
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- 2023
15. No genetic association between attention-deficit/hyperactivity disorder (ADHD) and Parkinson’s disease in nine ADHD candidate SNPs
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Geissler, Julia M., Romanos, Marcel, Gerlach, Manfred, Berg, Daniela, Schulte, Claudia, Nalls, Mike, Plagnol, Vincent, Hernandez, Dena G., Sharma, Manu, Sheerin, Una-Marie, Saad, Mohamad, Simón-Sánchez, Javier, Schulte, Claudia, Lesage, Suzanne, Sveinbjörnsdóttir, Sigurlaug, Arepalli, Sampath, Barker, Roger, Ben-Shlomo, Yoav, Berendse, Henk W., Berg, Daniela, Bhatia, Kailash, de Bie, Rob M. A., Biffi, Alessandro, Bloem, Bas, Bochdanovits, Zoltan, Bonin, Michael, Bras, Jose M., Brockmann, Kathrin, Brooks, Janet, Burn, David J., Charlesworth, Gavin, Chen, Honglei, Chinnery, Patrick F., Chong, Sean, Clarke, Carl E., Cookson, Mark R., Cooper, J. Mark, Corvol, Jean Christophe, Counsell, Carl, Damier, Philippe, Dartigues, Jean-François, Deloukas, Panos, Deuschl, Günther, Dexter, David T., van Dijk, Karin D., Dillman, Allissa, Durif, Frank, Dürr, Alexandra, Edkins, Sarah, Evans, Jonathan R., Foltynie, Thomas, Gao, Jianjun, Gardner, Michelle, Gibbs, J. Raphael, Goate, Alison, Gray, Emma, Guerreiro, Rita, Gústafsson, Ómar, Harris, Clare, van Hilten, Jacobus J., Hofman, Albert, Hollenbeck, Albert, Holton, Janice, Hu, Michele, Huang, Xuemei, Huber, Heiko, Hudson, Gavin, Hunt, Sarah E., Huttenlocher, Johanna, Illig, Thomas, Jónsson, Pálmi V., Lambert, Jean-Charles, Langford, Cordelia, Lees, Andrew, Lichtner, Peter, Limousin, Patricia, Lopez, Grisel, Lorenz, Delia, McNeill, Alisdair, Moorby, Catriona, Moore, Matthew, Morris, Huw R., Morrison, Karen E., Mudanohwo, Ese, O’Sullivan, Sean S., Pearson, Justin, Perlmutter, Joel S., Pétursson, Hjörvar, Pollak, Pierre, Post, Bart, Potter, Simon, Ravina, Bernard, Revesz, Tamas, Riess, Olaf, Rivadeneira, Fernando, Rizzu, Patrizia, Ryten, Mina, Sawcer, Stephen, Schapira, Anthony, Scheffer, Hans, Shaw, Karen, Shoulson, Ira, Sidransky, Ellen, Smith, Colin, Spencer, Chris C. A., Stefánsson, Hreinn, Steinberg, Stacy, Stockton, Joanna D., Strange, Amy, Talbot, Kevin, Tanner, Carlie M., Tashakkori-Ghanbaria, Avazeh, Tison, François, Trabzuni, Daniah, Traynor, Bryan J., Uitterlinden, André G., Velseboer, Daan, Vidailhet, Marie, Walker, Robert, van de Warrenburg, Bart, Wickremaratchi, Mirdhu, Williams, Nigel, Williams-Gray, Caroline H., Winder-Rhodes, Sophie, Stefánsson, Kári, Martinez, Maria, Hardy, John, Heutink, Peter, Brice, Alexis, Gasser, Thomas, Singleton, Andrew B., Wood, Nicholas W., and International Parkinson Disease Genomics Consortium members
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- 2017
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16. Exome sequencing establishes a gelsolin mutation as the cause of inherited bulbar‐onset neuropathy
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Caress, James B., Johnson, Janel O., Abramzon, Yevgeniya A., Hawkins, Gregory A., Gibbs, J. Raphael, Sullivan, Elizabeth A., Chahal, Chamanpreet S., and Traynor, Bryan J.
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- 2017
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17. Unexpected frequency of the pathogenic AR CAG repeat expansion in the general population.
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Zanovello, Matteo, Ibáñez, Kristina, Brown, Anna-Leigh, Sivakumar, Prasanth, Bombaci, Alessandro, Santos, Liana, Vugt, Joke J F A van, Narzisi, Giuseppe, Karra, Ramita, Scholz, Sonja W, Ding, Jinhui, Gibbs, J Raphael, Chiò, Adriano, Dalgard, Clifton, Weisburd, Ben, consortium, The American Genome Center (TAGC), Hanna, Michael G, Greensmith, Linda, Phatnani, Hemali, and Veldink, Jan H
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SPINOCEREBELLAR ataxia ,SPINAL muscular atrophy ,X chromosome ,NEUROMUSCULAR diseases ,DISEASE prevalence ,NUCLEOTIDE sequencing - Abstract
CAG repeat expansions in exon 1 of the AR gene on the X chromosome cause spinal and bulbar muscular atrophy, a male-specific progressive neuromuscular disorder associated with a variety of extra-neurological symptoms. The disease has a reported male prevalence of approximately 1:30 000 or less, but the AR repeat expansion frequency is unknown. We established a pipeline, which combines the use of the ExpansionHunter tool and visual validation, to detect AR CAG expansion on whole-genome sequencing data, benchmarked it to fragment PCR sizing, and applied it to 74 277 unrelated individuals from four large cohorts. Our pipeline showed sensitivity of 100% [95% confidence interval (CI) 90.8–100%], specificity of 99% (95% CI 94.2–99.7%), and a positive predictive value of 97.4% (95% CI 84.4–99.6%). We found the mutation frequency to be 1:3182 (95% CI 1:2309–1:4386, n = 117 734) X chromosomes—10 times more frequent than the reported disease prevalence. Modelling using the novel mutation frequency led to estimate disease prevalence of 1:6887 males, more than four times more frequent than the reported disease prevalence. This discrepancy is possibly due to underdiagnosis of this neuromuscular condition, reduced penetrance, and/or pleomorphic clinical manifestations. [ABSTRACT FROM AUTHOR]
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- 2023
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18. Age-associated changes in gene expression in human brain and isolated neurons
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Kumar, Azad, Gibbs, J. Raphael, Beilina, Alexandra, Dillman, Allissa, Kumaran, Ravindran, Trabzuni, Daniah, Ryten, Mina, Walker, Robert, Smith, Colin, Traynor, Bryan J., Hardy, John, Singleton, Andrew B., and Cookson, Mark R.
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- 2013
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19. ADORA1 mutations are not a common cause of Parkinsonʼs disease and dementia with Lewy bodies
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Blauwendraat, Cornelis, Nalls, Mike A., Federoff, Monica, Pletnikova, Olga, Ding, Jinhui, Letson, Christopher, Geiger, Joshua T., Gibbs, J. Raphael, Hernandez, Dena G., Troncoso, Juan C., Simón‐Sánchez, Javier, and Scholz, Sonja W.
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- 2017
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20. Establishing the role of rare coding variants in known Parkinson's disease risk loci
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Jansen, Iris E., Gibbs, J. Raphael, Nalls, Mike A., Price, T. Ryan, Lubbe, Steven, van Rooij, Jeroen, Uitterlinden, André G., Kraaij, Robert, Williams, Nigel M., Brice, Alexis, Hardy, John, Wood, Nicholas W., Morris, Huw R., Gasser, Thomas, Singleton, Andrew B., Heutink, Peter, and Sharma, Manu
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- 2017
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21. RNA Binding Activity of the Recessive Parkinsonism Protein DJ-1 Supports Involvement in Multiple Cellular Pathways
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van der Brug, Marcel P., Blackinton, Jeff, Chandran, Jayanth, Hao, Ling-Yang, Lal, Ashish, Mazan-Mamczarz, Krystyna, Martindale, Jennifer, Xie, Chengsong, Ahmad, Rili, Thomas, Kelly J., Beilina, Alexandra, Gibbs, J. Raphael, Ding, Jinhui, Myers, Amanda J., Zhan, Ming, Cai, Huaibin, Bonini, Nancy M., Gorospe, Myriam, and Cookson, Mark R.
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- 2008
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22. Genome-wide contribution of common short-tandem repeats to Parkinson's disease genetic risk.
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Bustos, Bernabe I, Billingsley, Kimberley, Blauwendraat, Cornelis, Gibbs, J Raphael, Gan-Or, Ziv, Krainc, Dimitri, Singleton, Andrew B, Lubbe, Steven J, (IPDGC), International Parkinson's Disease Genomics Consortium, and International Parkinson’s Disease Genomics Consortium (IPDGC)
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PARKINSON'S disease ,GENE frequency ,MICROSATELLITE repeats ,GENETIC disorders ,GENOME-wide association studies ,GENE expression - Abstract
Parkinson's disease is a complex neurodegenerative disorder with a strong genetic component, for which most known disease-associated variants are single nucleotide polymorphisms (SNPs) and small insertions and deletions (indels). DNA repetitive elements account for >50% of the human genome; however, little is known of their contribution to Parkinson's disease aetiology. While select short tandem repeats (STRs) within candidate genes have been studied in Parkinson's disease, their genome-wide contribution remains unknown. Here we present the first genome-wide association study of STRs in Parkinson's disease. Through a meta-analysis of 16 imputed genome-wide association study cohorts from the International Parkinson's Disease Genomic Consortium (IPDGC), totalling 39 087 individuals (16 642 cases and 22 445 controls of European ancestry), we identified 34 genome-wide significant STR loci (P < 5.34 × 10-6), with the strongest signal located in KANSL1 [chr17:44 205 351:[T]11, P = 3 × 10-39, odds ratio = 1.31 (95% confidence interval = 1.26-1.36)]. Conditional-joint analyses suggested that four significant STRs mapping nearby NDUFAF2, TRIML2, MIRNA-129-1 and NCOR1 were independent from known risk SNPs. Including STRs in heritability estimates increased the variance explained by SNPs alone. Gene expression analysis of STRs (eSTRs) in RNA sequencing data from 13 brain regions identified significant associations of STRs influencing the expression of multiple genes, including known Parkinson's disease genes. Further functional annotation of candidate STRs revealed that significant eSTRs within NUDFAF2 and ZSWIM7 overlap with regulatory features and are associated with change in the expression levels of nearby genes. Here, we show that STRs at known and novel candidate loci contribute to Parkinson's disease risk and have functional effects in disease-relevant tissues and pathways, supporting previously reported disease-associated genes and giving further evidence for their functional prioritization. These data represent a valuable resource for researchers currently dissecting Parkinson's disease risk loci. [ABSTRACT FROM AUTHOR]
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- 2023
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23. Chromosome 9p21 in amyotrophic lateral sclerosis in Finland: a genome-wide association study
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Laaksovirta, Hannu, Peuralinna, Terhi, Schymick, Jennifer C, Scholz, Sonja W, Lai, Shaoi-Lin, Myllykangas, Liisa, Sulkava, Raimo, Jansson, Lilja, Hernandez, Dena G, Gibbs, J Raphael, Nalls, Michael A, Heckerman, David, Tienari, Pentti J, and Traynor, Bryan J
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- 2010
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24. A pathway-based analysis provides additional support for an immune-related genetic susceptibility to Parkinsonʼs disease
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Holmans, Peter, Moskvina, Valentina, Jones, Lesley, Sharma, Manu, Vedernikov, Alexey, Buchel, Finja, Sadd, Mohamad, Bras, Jose M., Bettella, Francesco, Nicolaou, Nayia, Simón-Sánchez, Javier, Mittag, Florian, Gibbs, J. Raphael, Schulte, Claudia, Durr, Alexandra, Guerreiro, Rita, Hernandez, Dena, Brice, Alexis, Stefánsson, Hreinn, Majamaa, Kari, Gasser, Thomas, Heutink, Peter, Wood, Nicholas W., Martinez, Maria, Singleton, Andrew B., Nalls, Michael A., Hardy, John, Morris, Huw R., Williams, Nigel M., Arepalli, Sampath, Barker, Roger, Barrett, Jeffrey, Ben-Shlomo, Yoav, Berendse, Henk W., Berg, Daniela, Bhatia, Kailash, de Bie, Rob M.A., Biffi, Alessandro, Bloem, Bas, Brice, Alexis, Bochdanovits, Zoltan, Bonin, Michael, Bras, Jose M., Brockmann, Kathrin, Brooks, Janet, Burn, David J., Charlesworth, Gavin, Chen, Honglei, Chinnery, Patrick F., Chong, Sean, Clarke, Carl E., Cookson, Mark R., Cooper, Jonathan M., Corvol, Jen-Christophe, Counsell, Carl, Damier, Philippe, Dartigues, Jean Francois, Deloukas, Panagiotis, Deuschl, Günther, Dexter, David T., van Dijk, Karin D., Dillman, Allissa, Durif, Frank, Durr, Alexandra, Edkins, Sarah, Evans, Jonathan R., Foltynie, Thomas, Gao, Jianjun, Gardner, Michelle, Gasser, Thomas, Gibbs, J. Raphael, Goate, Alison, Gray, Emma, Guerreiro, Rita, Gústafsson, Ómar, Hardy, John, Harris, Clare, Hernandez, Dena G., Heutink, Peter, van Hilten, Jacobus J., Hofman, Albert, Hollenbeck, Albert, Holmans, Peter, Holton, Janice, Hu, Michele, Huber, Heiko, Hudson, Gavin, Hunt, Sarah E., Huttenlocher, Johanna, Illig, Thomas, Langford, Cordelia, Lees, Andrew, Lesage, Suzanne, Lichtner, Peter, Limousin, Patricia, Lopez, Grisel, Lorenz, Delia, Martinez, Maria, McNeill, Alisdair, Moorby, Catriona, Moore, Matthew, Morris, Huw, Morrison, Karen E., Moskvina, Valentina, Mudanohwo, Ese, Nalls, Michael A., Pearson, Justin, Perlmutter, Joel S., Pétursson, Hjörvar, Plagnol, Vincent, Pollak, Pierre, Post, Bart, Potter, Simon, Ravina, Bernard, Revesz, Tamas, Riess, Olaf, Rivadeneira, Fernando, Rizzu, Patrizia, Ryten, Mina, Saad, Mohamad, Sawcer, Stephen, Schapira, Anthony, Scheffer, Hans, Sharma, Manu, Shaw, Karen, Sheerin, Una-Marie, Shoulson, Ira, Schulte, Claudia, Sidransky, Ellen, Simón-Sánchez, Javier, Singleton, Andrew B., Smith, Colin, Stefánsson, Hreinn, Stefánsson, Kári, Steinberg, Stacy, Stockton, Joanna D., Sveinbjornsdottir, Sigurlaug, Talbot, Kevin, Tanner, Carlie M., Tashakkori-Ghanbaria, Avazeh, Tison, François, Trabzuni, Daniah, Traynor, Bryan J., Uitterlinden, André G., Velseboer, Daan, Vidailhet, Marie, Walker, Robert, van de Warrenburg, Bart, Wickremaratchi, Mirdhu, Williams, Nigel, Williams-Gray, Caroline H., Winder-Rhodes, Sophie, and Wood, Nicholas
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- 2013
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25. Association of a Novel ACTA1 Mutation With a Dominant Progressive Scapuloperoneal Myopathy in an Extended Family
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Zukosky, Kristen, Meilleur, Katherine, Traynor, Bryan J., Dastgir, Jahannaz, Medne, Livija, Devoto, Marcella, Collins, James, Rooney, Jachinta, Zou, Yaqun, Yang, Michele L., Gibbs, J. Raphael, Meier, Markus, Stetefeld, Joerg, Finkel, Richard S., Schessl, Joachim, Elman, Lauren, Felice, Kevin, Ferguson, Toby A., Ceyhan-Birsoy, Ozge, Beggs, Alan H., Tennekoon, Gihan, Johnson, Janel O., and Bönnemann, Carsten G.
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- 2015
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26. A Genome-Wide Association Study of Myasthenia Gravis
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Renton, Alan E., Pliner, Hannah A., Provenzano, Carlo, Evoli, Amelia, Ricciardi, Roberta, Nalls, Michael A., Marangi, Giuseppe, Abramzon, Yevgeniya, Arepalli, Sampath, Chong, Sean, Hernandez, Dena G., Johnson, Janel O., Bartoccioni, Emanuela, Scuderi, Flavia, Maestri, Michelangelo, Gibbs, J. Raphael, Errichiello, Edoardo, Chiò, Adriano, Restagno, Gabriella, Sabatelli, Mario, Macek, Mark, Scholz, Sonja W., Corse, Andrea, Chaudhry, Vinay, Benatar, Michael, Barohn, Richard J., McVey, April, Pasnoor, Mamatha, Dimachkie, Mazen M., Rowin, Julie, Kissel, John, Freimer, Miriam, Kaminski, Henry J., Sanders, Donald B., Lipscomb, Bernadette, Massey, Janice M., Chopra, Manisha, Howard, James F., Jr, Koopman, Wilma J., Nicolle, Michael W., Pascuzzi, Robert M., Pestronk, Alan, Wulf, Charlie, Florence, Julaine, Blackmore, Derrick, Soloway, Aimee, Siddiqi, Zaeem, Muppidi, Srikanth, Wolfe, Gil, Richman, David, Mezei, Michelle M., Jiwa, Theresa, Oger, Joel, Drachman, Daniel B., and Traynor, Bryan J.
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- 2015
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27. Whole-genome sequencing to understand the genetic architecture of common gene expression and biomarker phenotypes
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Wood, Andrew R., Tuke, Marcus A., Nalls, Mike, Hernandez, Dena, Gibbs, J. Raphael, Lin, Haoxiang, Xu, Christopher S., Li, Qibin, Shen, Juan, Jun, Goo, Almeida, Marcio, Tanaka, Toshiko, Perry, John R. B., Gaulton, Kyle, Rivas, Manny, Pearson, Richard, Curran, Joanne E., Johnson, Matthew P., Göring, Harald H. H., Duggirala, Ravindranath, Blangero, John, Mccarthy, Mark I., Bandinelli, Stefania, Murray, Anna, Weedon, Michael N., Singleton, Andrew, Melzer, David, Ferrucci, Luigi, and Frayling, Timothy M
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- 2015
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28. Identification of candidate parkinson disease genes by integrating genome-wide association study, expression, and epigenetic data sets
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Kia, Demis A., Zhang, David, Guelfi, Sebastian, Manzoni, Claudia, Hubbard, Leon, Reynolds, Regina H., Botía, Juan, Ryten, Mina, Ferrari, Raffaele, Lewis, Patrick A., Williams, Nigel, Trabzuni, Daniah, Hardy, John, Wood, Nicholas W., Noyce, Alastair J., Kaiyrzhanov, Rauan, Middlehurst, Ben, Tan, Manuela, Houlden, Henry, Morris, Huw R., Plun-Favreau, Helene, Holmans, Peter, Bras, Jose, PhD, John Quinn, Mok, Kin Y., Kinghorn, Kerri J., Billingsley, Kimberley, Lewis, Patrick, Schreglmann, Sebastian, Guerreiro, Rita, Lovering, Ruth, R'Bibo, Lea, Rizig, Mie, Escott-Price, Valentina, Chelban, Viorica, Foltynie, Thomas, Brice, Alexis, Danjou, Fabrice, Lesage, Suzanne, Corvol, Jean-Christophe, Martinez, Maria, Schulte, Claudia, Brockmann, Kathrin, Simón-Sánchez, Javier, Heutink, Peter, Rizzu, Patrizia, Sharma, Manu, Gasser, Thomas, Nicolas, Aude, Cookson, Mark R., Bandres-Ciga, Sara, Blauwendraat, Cornelis, Craig, David W., Faghri, Faraz, Gibbs, J. Raphael, Hernandez, Dena G., Van Keuren-Jensen, Kendall, Shulman, Joshua M., Leonard, Hampton L., Nalls, Mike A., Robak, Laurie, Lubbe, Steven, Finkbeiner, Steven, Mencacci, Niccolo E., Lungu, Codrin, Singleton, Andrew B, Scholz, Sonja W., Reed, Xylena, Alcalay, Roy N., Gan-Or, Ziv, Rouleau, Guy A., Krohn, Lynne, van Hilten, Jacobus J., Marinus, Johan, Adarmes-Gómez, Astrid D., Aguilar, Miquel, Alvarez, Ignacio, Alvarez, Victoria, Javier Barrero, Francisco, Bergareche Yarza, Jesús A., Bernal-Bernal, Inmaculada, Blazquez, Marta, Bonilla-Toribio, Marta, Botía, Juan A., Boungiorno, María T., Buiza-Rueda, Dolores, Càmara, Ana, Carrillo, Fátima, Carrión-Claro, Mario, Cerdan, Debora, Clarimón, Jordi, Compta, Yaroslau, Diez-Fairen, Monica, Dols-Icardo, Oriol, Duarte, Jacinto, Duran, Raquel, Escamilla-Sevilla, Francisco, Ezquerra, Mario, Feliz, Cici, Fernàndez, Manel, Fernàndez-Santiago, Rubén, Garcia, Ciara, García-Ruiz, Pedro, Gómez-Garre, Pilar, Gomez Heredia, Maria J., Gonzalez-Aramburu, Isabel, Pagola, Ana G., Hoenicka, Janet, Infante, Jon, Jimenez-Escrig, Adriano, Kulisevsky, Jaime, Labrador-Espinosa, Miguel A., Lopez-Sendon, Jose Luis, Arregui, Adolfo López de Munain, Macias, Daniel, Torres, Irene Martínez, Marín, Juan, Marti, Maria Jose, Martínez-Castrillo, Juan Carlos, Mèndez-del-Barrio, Carlota, González, Manuel Menéndez, Adolfo Mínguez, Marina Mata, Mir, Pablo, Rezola, Elisabet Mondragon, Muñoz, Esteban, Pagonabarraga, Javier, Pastor, Pau, Errazquin, Francisco Perez, Perinán-Tocino, Teresa, Ruiz-Martínez, Javier, Ruz, Clara, Rodriguez, Antonio Sanchez, Sierra, María, Suarez-Sanmartin, Esther, Tabernero, Cesar, Tartari, Juan Pablo, Tejera-Parrado, Cristina, Tolosa, Eduard, Valldeoriola, Francesc, Vargas-González, Laura, Vela, Lydia, Vives, Francisco, Zimprich, Alexander, Pihlstrom, Lasse, Toft, Mathias, Koks, Sulev, Taba, Pille, Hassin-Baer, Sharon, Weale, Michael, Ramasamy, Adaikalavan, Smith, Colin, Guelfi, Manuel Sebastian, D'sa, Karishma, Forabosco, Paola, Botiá, Juan A., and Universidad de Cantabria
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Candidate gene ,Protein catabolic process ,Gene Expression ,Genome-wide association study ,Computational biology ,Biology ,Epigenesis, Genetic ,03 medical and health sciences ,0302 clinical medicine ,Databases, Genetic ,Humans ,Online First ,030212 general & internal medicine ,Epigenetics ,Gene ,Genetic Association Studies ,Genetic association ,Original Investigation ,Research ,Parkinson Disease ,Protein ubiquitination ,Neurology (clinical) ,Candidate Disease Gene ,030217 neurology & neurosurgery ,Comments ,Genome-Wide Association Study - Abstract
Key Points Question What genes and genomic processes underlie risk of sporadic Parkinson disease? Findings This genetic association study integrated Parkinson disease genome-wide association study data and brain-derived gene regulation data using various complementary bioinformatic tools and identified 11 candidate genes with evidence of disease-associated regulatory changes. Coexpression and protein level analyses of these genes demonstrated a significant functional association with known mendelian Parkinson disease genes. Meaning This study suggests that gene regulation data may be used to identify candidate genes and pathways involved in sporadic Parkinson disease., Importance Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number of loci shown reliably to be associated with increased risk of disease. Improved understanding of the underlying genes and mechanisms at these loci will be key to understanding the pathogenesis of PD. Objective To investigate what genes and genomic processes underlie the risk of sporadic PD. Design and Setting This genetic association study used the bioinformatic tools Coloc and transcriptome-wide association study (TWAS) to integrate PD case-control GWAS data published in 2017 with expression data (from Braineac, the Genotype-Tissue Expression [GTEx], and CommonMind) and methylation data (derived from UK Parkinson brain samples) to uncover putative gene expression and splicing mechanisms associated with PD GWAS signals. Candidate genes were further characterized using cell-type specificity, weighted gene coexpression networks, and weighted protein-protein interaction networks. Main Outcomes and Measures It was hypothesized a priori that some genes underlying PD loci would alter PD risk through changes to expression, splicing, or methylation. Candidate genes are presented whose change in expression, splicing, or methylation are associated with risk of PD as well as the functional pathways and cell types in which these genes have an important role. Results Gene-level analysis of expression revealed 5 genes (WDR6 [OMIM 606031], CD38 [OMIM 107270], GPNMB [OMIM 604368], RAB29 [OMIM 603949], and TMEM163 [OMIM 618978]) that replicated using both Coloc and TWAS analyses in both the GTEx and Braineac expression data sets. A further 6 genes (ZRANB3 [OMIM 615655], PCGF3 [OMIM 617543], NEK1 [OMIM 604588], NUPL2 [NCBI 11097], GALC [OMIM 606890], and CTSB [OMIM 116810]) showed evidence of disease-associated splicing effects. Cell-type specificity analysis revealed that gene expression was overall more prevalent in glial cell types compared with neurons. The weighted gene coexpression performed on the GTEx data set showed that NUPL2 is a key gene in 3 modules implicated in catabolic processes associated with protein ubiquitination and in the ubiquitin-dependent protein catabolic process in the nucleus accumbens, caudate, and putamen. TMEM163 and ZRANB3 were both important in modules in the frontal cortex and caudate, respectively, indicating regulation of signaling and cell communication. Protein interactor analysis and simulations using random networks demonstrated that the candidate genes interact significantly more with known mendelian PD and parkinsonism proteins than would be expected by chance. Conclusions and Relevance Together, these results suggest that several candidate genes and pathways are associated with the findings observed in PD GWAS studies., This genetic association study investigates what genes and genomic processes underlie the risk of sporadic Parkinson disease.
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- 2021
29. ATXN2 intermediate expansions in amyotrophic lateral sclerosis.
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Glass, Jonathan D, Dewan, Ramita, Ding, Jinhui, Gibbs, J Raphael, Dalgard, Clifton, Keagle, Pamela J, Shankaracharya, García-Redondo, Alberto, Traynor, Bryan J, Chia, Ruth, and Landers, John E
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LEWY body dementia ,AMYOTROPHIC lateral sclerosis ,RESEARCH funding ,FRONTOTEMPORAL dementia ,PHENOTYPES - Abstract
Intermediate CAG (polyQ) expansions in the gene ataxin-2 (ATXN2) are now recognized as a risk factor for amyotrophic lateral sclerosis. The threshold for increased risk is not yet firmly established, with reports ranging from 27 to 31 repeats. We investigated the presence of ATXN2 polyQ expansions in 9268 DNA samples collected from people with amyotrophic lateral sclerosis, amyotrophic lateral sclerosis with frontotemporal dementia, frontotemporal dementia alone, Lewy body dementia and age matched controls. This analysis confirmed ATXN2 intermediate polyQ expansions of ≥31 as a risk factor for amyotrophic lateral sclerosis with an odds ratio of 6.31. Expansions were an even greater risk for amyotrophic lateral sclerosis with frontotemporal dementia (odds ratio 27.59) and a somewhat lesser risk for frontotemporal dementia alone (odds ratio 3.14). There was no increased risk for Lewy body dementia. In a subset of 1362 patients with amyotrophic lateral sclerosis with complete clinical data, we could not confirm previous reports of earlier onset of amyotrophic lateral sclerosis or shorter survival in 25 patients with expansions. These new data confirm ≥31 polyQ repeats in ATXN2 increase the risk for amyotrophic lateral sclerosis, and also for the first time show an even greater risk for amyotrophic lateral sclerosis with frontotemporal dementia. The lack of a more aggressive phenotype in amyotrophic lateral sclerosis patients with expansions has implications for ongoing gene-silencing trials for amyotrophic lateral sclerosis. [ABSTRACT FROM AUTHOR]
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- 2022
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30. TBK1 is associated with ALS and ALS-FTD in Sardinian patients
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Logullo, Francesco O., Simone, Isabella, Logroscino, Giancarlo, Salvi, Fabrizio, Bartolomei, Ilaria, Capasso, Margherita, Caponnetto, Claudia, Mandich, Paolo, Mancardi, Gianluigi, Origone, Paola, Conforti, Francesca L., Vita, Giuseppe, Messina, Sonia, Russo, Massimo, Mora, Gabriele, Marinou, Kalliopi, Sideri, Riccardo, Lunetta, Christian, Penco, Silvana, Mosca, Lorena, Pinter, Giuseppe Lauria, Corbo, Massimo, Riva, Nilo, Carrera, Paola, Volanti, Paolo, Tremolizzo, Lucio, Ferrarese, Carlo, Fini, Nicola, Fasano, Antonio, Monsurrò, Maria Rosaria, Tedeschi, Gioacchino, Trojsi, Francesca, Piccirillo, Giovanni, Cristillo, Viviana, Mazzini, Letizia, D'Alfonso, Sandra, Bersano, Anna, Corrado, Lucia, Bagarotti, Alessandra, La Bella, Vincenzo, Spataro, Rossella, Colletti, Tiziana, Sabatelli, Mario, Zollino, Marcella, Conte, Amelia, Luigetti, Marco, Lattante, Serena, Marangi, Giuseppe, Santarelli, Marialuisa, Petrucci, Antonio, Giannini, Fabio, Battistini, Stefania, Ricci, Claudia, Benigni, Michele, Restagno, Gabriella, Casale, Federico, Marrali, Giuseppe, Fuda, Giuseppe, Ossola, Irene, Cammarosano, Stefania, Ilardi, Antonio, Bertuzzo, Davide, Tanel, Raffaella, Pisano, Fabrizio, Costantino, Emanuela, Pani, Carla, Puddu, Roberta, Caredda, Carla, Piras, Valeria, Tranquilli, Stefania, Cuccu, Stefania, Corongiu, Daniela, Melis, Maurizio, Milia, Antonio, Pirisi, Angelo, Parish, Leslie D., Ortu, Enzo, Borghero, Giuseppe, Pugliatti, Maura, Marrosu, Francesco, Marrosu, Maria Giovanna, Murru, Maria Rita, Floris, Gianluca, Cannas, Antonino, Occhineri, Patrizia, Cau, Tea B., Loi, Daniela, Ticca, Anna, Traccis, Sebastiano, Manera, Umberto, Canosa, Antonio, Moglia, Cristina, Calvo, Andrea, Barberis, Marco, Brunetti, Maura, Gibbs, J. Raphael, Renton, Alan E., Errichiello, Edoardo, Zoledziewska, Magdalena, Mulas, Antonella, Qian, Yong, Din, Jun, Pliner, Hannah A., Traynor, Bryan J., and Chiò, Adriano
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- 2016
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31. Mutation analysis of the MS4A and TREM gene clusters in a case-control Alzheimer's disease data set
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Ghani, Mahdi, Sato, Christine, Kakhki, Erfan Ghani, Gibbs, J. Raphael, Traynor, Bryan, St George-Hyslop, Peter, and Rogaeva, Ekaterina
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- 2016
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32. Mutations in the CHCHD10 gene are a common cause of familial amyotrophic lateral sclerosis
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Johnson, Janel O., Glynn, Shannon M., Gibbs, J. Raphael, Nalls, Mike A., Sabatelli, Mario, Restagno, Gabriella, Drory, Vivian E., Chiò, Adriano, Rogaeva, Ekaterina, and Traynor, Bryan J.
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- 2014
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33. Investigation of Autosomal Genetic Sex Differences in Parkinson's Disease
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Blauwendraat, Cornelis, Iwaki, Hirotaka, Gibbs, Jesse R, Bras, Jose, Guerreiro, Rita, Lubbe, Steven, Troycoco, Timothy, Finkbeiner, Steven, Mencacci, Niccolo E, Lungu, Codrin, Singleton, Andrew B, Scholz, Sonja W, Reed, Xylena, Hernandez, Dena Michelle Godwin, Uitti, Ryan J, Ross, Owen A, Grenn, Francis P, Moore, Anni, Alcalay, Roy N, Wszolek, Zbigniew K, Gan-Or, Ziv, Rouleau, Guy A, Krohn, Lynne, Mufti, Kheireddin, Ruskey, Jennifer A, van Hilten, Jacobus J, Marinus, Johan, Adarmes-Gómez, Astrid D, Aguilar, Miquel, Alvarez, Ignacio, Alvarez, Victoria, Barrero, Francisco Javier, Yarza, Jesús Alberto Bergareche, Bernal-Bernal, Inmaculada, Blazquez, Marta, Pihlstrøm, Lasse, Bonilla-Toribio, Marta, Botía, Juan A, Boungiorno, María Teresa, Buiza-Rueda, Dolores, Cámara, Ana, Carrillo, Fátima, Carrión-Claro, Mario, Cerdan, Debora, Clarimón, Jordi, Compta, Yaroslau, Toft, Mathias, Diez-Fairen, Monica, Dols-Icardo, Oriol, Duarte, Jacinto, Duran, Raquel, Escamilla-Sevilla, Francisco, Ezquerra, Mario, Feliz, Cici, Fernández, Manel, Fernández-Santiago, Rubén, Garcia, Ciara, García-Ruiz, Pedro, Gómez-Garre, Pilar, Heredia, Maria Jose Gomez, Gonzalez-Aramburu, Isabel, Pagola, Ana Gorostidi, Hoenicka, Janet, Infante, Jon, Jesús, Silvia, Jimenez-Escrig, Adriano, Kulisevsky, Jaime, Labrador-Espinosa, Miguel A, Lopez-Sendon, Jose Luis, de Munain Arregui, Adolfo López, Macias, Daniel, Torres, Irene Martínez, Marín, Juan, Marti, Maria Jose, Martínez-Castrillo, Juan Carlos, Méndez-Del-Barrio, Carlota, González, Manuel Menéndez, Schulte, Claudia, Mata, Marina, Mínguez, Adolfo, Mir, Pablo, Rezola, Elisabet Mondragon, Muñoz, Esteban, Pagonabarraga, Javier, Pastor, Pau, Errazquin, Francisco Perez, Periñán-Tocino, Teresa, Ruiz-Martínez, Javier, Brockmann, Kathrin, Ruz, Clara, Rodriguez, Antonio Sanchez, Sierra, María, Suarez-Sanmartin, Esther, Tabernero, Cesar, Tartari, Juan Pablo, Tejera-Parrado, Cristina, Tolosa, Eduard, Valldeoriola, Francesc, Vargas-González, Laura, Sharma, Manu, Vela, Lydia, Vives, Francisco, Zimprich, Alexander, Pihlstrom, Lasse, Taba, Pille, Koks, Sulev, Hassin-Baer, Sharon, Majamaa, Kari, Siitonen, Ari, Makarious, Mary B, Tienari, Pentti, Okubadejo, Njideka U, Ojo, Oluwadamilola O, Kaiyrzhanov, Rauan, Shashkin, Chingiz, Zharkinbekova, Nazira, Akhmetzhanov, Vadim, Kaishybayeva, Gulnaz, Karimova, Altynay, Khaibullin, Talgat, Lynch, Timothy L, Eerola-Rautio, Johanna, Tienari, Pentti J, Grosset, Donald G, Lesage, Suzanne, Corvol, Jean-Christophe, Brice, Alexis, Wood, Nick, Hardy, John, Bandres-Ciga, Sara, Heutink, Peter, Gasser, Thomas, Morris, Huw R, Noyce, Alastair J, Nalls, Mike A, Consortium, and the International Parkinson's Disease Genomics, Leonard, Hampton L, Middlehurst, Ben, Kia, Demis A, Tan, Manuela, Houlden, Henry, Storm, Catherine S, Plun-Favreau, Helene, Holmans, Peter, Trabzuni, Daniah, Quinn, John, Bubb, Vivien, Mok, Kin Y, Kinghorn, Kerri J, Wood, Nicholas W, Lewis, Patrick, Schreglmann, Sebastian R, Lovering, Ruth, R'Bibo, Lea, Manzoni, Claudia, Lake, Julie, Rizig, Mie, Ryten, Mina, Guelfi, Sebastian, Escott-Price, Valentina, Chelban, Viorica, Foltynie, Thomas, Williams, Nigel, Morrison, Karen E, Clarke, Carl, Harvey, Kirsten, Jacobs, Benjamin M, Danjou, Fabrice, Martinez, Maria, Simón-Sánchez, Javier, Rizzu, Patrizia, Schneider, Susanne A, Cookson, Mark R, Craig, David W, Billingsley, Kimberley, Kim, Jonggeol J, Narendra, Derek P, Faghri, Faraz, Gibbs, J Raphael, Van Keuren-Jensen, Kendall, Shulman, Joshua M, Robak, Laurie, Universidad de Cantabria, HUS Neurocenter, Neurologian yksikkö, Department of Neurosciences, University of Helsinki, Clinicum, Research Programs Unit, and Eija Pirinen / Principal Investigator
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0301 basic medicine ,Male ,Genotype ,EFFICIENT ,Physiology ,Genome-wide association study ,Disease ,Biology ,Genetic correlation ,3124 Neurology and psychiatry ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,genetics [Parkinson Disease] ,Genetic variation ,Humans ,Genetic Predisposition to Disease ,ddc:610 ,Parkinson Disease/genetics ,METAANALYSIS ,Research Articles ,Genetic association ,Aged ,RISK ,Sex Characteristics ,Autosome ,3112 Neurosciences ,Parkinson Disease ,Heritability ,Middle Aged ,Genetic architecture ,3. Good health ,030104 developmental biology ,Neurology ,Female ,GENDER ,Neurology (clinical) ,030217 neurology & neurosurgery ,Research Article ,Genome-Wide Association Study - Abstract
Methods: In an effort to study sex-specific genetic factors associated with PD, we explored 2 large genetic datasets from the International Parkinson?s Disease Genomics Consortium and the UK Biobank consisting of 13,020male PD cases, 7,936 paternal proxy cases, 89,660 male controls, 7,947 female PD cases, 5,473 maternal proxy cases, and 90,662 female controls. We performed GWASmeta-analyses to identify distinct patterns of genetic risk contributing to disease inmale versus female PD cases. Results: In total, 19 genomewide significant regions were identified and no sex-specific effects were observed. A high genetic correlation between the male and female PD GWAS were identified (rg = 0.877) and heritability estimates were identical between male and female PD cases (~ 20%). Interpretation: We did not detect any significant genetic differences between male or female PD cases. Our study does not support the notion that common genetic variation on the autosomes could explain the difference in prevalence of PD between males and females cases at least when considering the current sample size under study. Further studies are warranted to investigate the genetic architecture of PD explained by X and Y chromosomes and further evaluate environmental effects that could potentially contribute to PD etiology in male versus female patients. FUNDING: This work was supported in part by the Intramural Research Programs of the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Aging (NIA), and the National Institute of Environmental Health Sciences both part of the National Institutes of Health, Department of Health and Human Services; Project numbers 1ZIA-NS003154, Z01-AG000949-02, and Z01-ES101986. In addition, this work was supported by the Department of Defense (award W81XWH-09-2-0128), and The Michael J. Fox Foundation for Parkinson’s Research. This work was supported by National Institutes of Health grants R01NS037167, R01CA141668, and P50NS071674, American Parkinson Disease Association (APDA); Barnes Jewish Hospital Foundation; Greater St Louis Chapter of the APDA. The KORA (Cooperative Research in the Region of Augsburg) research platform was started and financed by the Forschungszentrum für Umwelt und Gesundheit, which is funded by the German Federal Ministry of Education, Science, Research, and Technology and by the State of Bavaria. This study was also funded by the German Federal Ministry of Education and Research (BMBF) under the funding code 031A430A, the EU Joint Programme - Neurodegenerative Diseases Research (JPND) project under the aegis of JPND -www.jpnd.eu – through Germany, BMBF, funding code 01ED1406 and iMed – the Helmholtz Initiative on Personalized Medicine. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD, USA (http://biowulf.nih.gov), and DNA panels, samples, and clinical data from the National Institute of Neurological Disorders and Stroke Human Genetics Resource Center DNA and Cell Line Repository. People who contributed samples are acknowledged in descriptions of every panel on the repository website. We thank P. Tienari (Molecular Neurology Programme, Biomedicum, University of Helsinki), T. Peuralinna (Department of Neurology, Helsinki University Central Hospital), L. Myllykangas (Folkhalsan Institute of Genetics and Department of Pathology, University of Helsinki), and R. Sulkava (Department of Public Health and General Practice Division of Geriatrics, University of Eastern Finland) for the Finnish controls (Vantaa85+ GWAS data). This study was also funded by the Sigrid Juselius Foundation (KM). We used genomewide association data generated by the Wellcome Trust Case–Control Consortium 2 (WTCCC2) from UK patients with Parkinson’s disease and UK control individuals from the 1958 Birth Cohort and National Blood Service. UK population control data was made available through WTCCC1. As with previous IPDGC efforts, this study makes use of data generated by the Wellcome Trust Case-Control Consortium. A full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk. Funding for the project was provided by the Wellcome Trust under awards 076113, 085475, and 090355. This study was also supported by Parkinson’s UK (grants 8047 and J-0804) and the Medical Research Council (G0700943 and G1100643). Sequencing and genotyping done in McGill University was supported by grants from the Michael J. Fox Foundation, the Canadian Consortium on Neurodegeneration in Aging (CCNA), the Canada First Research Excellence Fund (CFREF), awarded to McGill University for the Healthy Brains for Healthy Lives (HBHL) program and Parkinson’s Society Canada. The access to part of the participants at McGill has been made possible thanks to the Quebec Parkinson’s Network (http://rpq-qpn.ca/en). We thank the Quebec Parkinson’s Network (http://rpq-qpn.org) and its members. Harvard NeuroDiscovery Biomarker Study (HBS) is a collaboration of HBS investigators and funded through philanthropy and NIH and Non-NIH funding sources. The HBS Investigators have not participated in reviewing the data analysis or content of the manuscript. PPMI – a public-private partnership – is funded by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, the full names of all of the PPMI funding partners can be found at www.ppmi-info.org/ fundingpartners. The PPMI Investigators have not participated in reviewing the data analysis or content of the manuscript. For up-to-date information on the study, visit www.ppmi-info.org. Parkinson’s Disease Biomarker Program (PDBP) consortium is supported by the National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health. A full list of PDBP investigators can be found at https://pdbp.ninds.nih.gov/ policy. The PDBP Investigators have not participated in reviewing the data analysis or content of the manuscript
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- 2021
34. DYT16, a novel young-onset dystonia-parkinsonism disorder: identification of a segregating mutation in the stress-response protein PRKRA
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Camargos, Sarah, Scholz, Sonja, Simón-Sánchez, Javier, Paisán-Ruiz, Coro, Lewis, Patrick, Hernandez, Dena, Ding, Jinhui, Gibbs, J Raphael, Cookson, Mark R, Bras, Jose, Guerreiro, Rita, Oliveira, Catarina Resende, Lees, Andrew, Hardy, John, Cardoso, Francisco, and Singleton, Andrew B
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- 2008
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35. Structural genomic variation in ischemic stroke
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Matarin, Mar, Simon-Sanchez, Javier, Fung, Hon-Chung, Scholz, Sonja, Gibbs, J. Raphael, Hernandez, Dena G., Crews, Cynthia, Britton, Angela, Wavrant De Vrieze, Fabienne, Brott, Thomas G., Brown, Jr., Robert D., Worrall, Bradford B., Silliman, Scott, Case, L. Douglas, Hardy, John A., Rich, Stephen S., Meschia, James F., and Singleton, Andrew B.
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- 2008
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36. Association of a common genetic variant with Parkinson's disease is mediated by microglia.
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Langston, Rebekah G., Beilina, Alexandra, Reed, Xylena, Kaganovich, Alice, Singleton, Andrew B., Blauwendraat, Cornelis, Gibbs, J. Raphael, and Cookson, Mark R.
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MICROGLIA ,PARKINSON'S disease ,GENETIC variation ,GENOME-wide association studies ,SUBSTANTIA nigra ,DARDARIN - Abstract
Studies of multiple neurodegenerative disorders have identified many genetic variants that are associated with risk of disease throughout a lifetime. For example, Parkinson's disease (PD) risk is attributed in part to both coding mutations in the leucine-rich repeat kinase 2 (LRRK2) gene and to a common noncoding variation in the 5′ region of the LRRK2 locus, as identified by genome-wide association studies (GWAS). However, the mechanisms linking GWAS variants to pathogenicity are largely unknown. Here, we found that the influence of PD-associated noncoding variation on LRRK2 expression is specifically propagated through microglia and not by other cell types that express LRRK2 in the human brain. We find microglia-specific regulatory chromatin regions that modulate the LRRK2 expression in human frontal cortex and substantia nigra and confirm these results in a human-induced pluripotent stem cell–derived microglia model. We showed, using a large-scale clustered regularly interspaced short palindromic repeats interference (CRISPRi) screen, that a regulatory DNA element containing the single-nucleotide variant rs6581593 influences the LRRK2 expression in microglia. Our study demonstrates that cell type should be considered when evaluating the role of noncoding variation in disease pathogenesis and sheds light on the mechanism underlying the association of the 5′ region of LRRK2 with PD risk. Microglia modulates PD risk: Previous studies have identified variants in the LRRK2 gene that are associated with an increased risk of developing Parkinson's disease (PD). Here, Langston and colleagues studied the mechanisms of LRRK2 variants to PD and showed that the disease risk is determined by microglial cells. Studying PD-associated LRRK2 variants in patient-derived tissue and iPSC-derived microglia, the authors identified a quantitative trait in microglia, suggesting that, although this cell type expresses LRRK2 in lower amounts compared to other cell types, it might be critical for determining the PD risk. The cell type–specific baseline expression and effect on disease pathophysiology might not be predictive of the mechanisms mediating this and other disease-associated variants in noncoding gene regions. [ABSTRACT FROM AUTHOR]
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- 2022
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37. Heterozygous PRKN mutations are common but do not increase the risk of Parkinson's disease.
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Zhu, William, Huang, Xiaoping, Yoon, Esther, Bandres-Ciga, Sara, Blauwendraat, Cornelis, Billingsley, Kimberly J, Cade, Joshua H, Wu, Beverly P, Williams, Victoria H, Schindler, Alice B, Brooks, Janet, Gibbs, J Raphael, Hernandez, Dena G, Ehrlich, Debra, Singleton, Andrew B, and Narendra, Derek P
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ENZYME metabolism ,GENETIC mutation ,PARKINSON'S disease ,ENZYMES ,RESEARCH funding ,ADENOSINE monophosphate ,LONGITUDINAL method - Abstract
PRKN mutations are the most common recessive cause of Parkinson's disease and are a promising target for gene and cell replacement therapies. Identification of biallelic PRKN patients at the population scale, however, remains a challenge, as roughly half are copy number variants and many single nucleotide polymorphisms are of unclear significance. Additionally, the true prevalence and disease risk associated with heterozygous PRKN mutations is unclear, as a comprehensive assessment of PRKN mutations has not been performed at a population scale. To address these challenges, we evaluated PRKN mutations in two cohorts with near complete genotyping of both single nucleotide polymorphisms and copy number variants: the NIH-PD + AMP-PD cohort, the largest Parkinson's disease case-control cohort with whole genome sequencing data from 4094 participants, and the UK Biobank, the largest cohort study with whole exome sequencing and genotyping array data from 200 606 participants. Using the NIH-PD participants, who were genotyped using whole genome sequencing, genotyping array, and multi-plex ligation-dependent probe amplification, we validated genotyping array for the detection of copy number variants. Additionally, in the NIH-PD cohort, functional assays of patient fibroblasts resolved variants of unclear significance in biallelic carriers and suggested that cryptic loss of function variants in monoallelic carriers are not a substantial confounder for association studies. In the UK Biobank, we identified 2692 PRKN copy number variants from genotyping array data from nearly half a million participants (the largest collection to date). Deletions or duplications involving exon 2 accounted for roughly half of all copy number variants and the vast majority (88%) involved exons 2, 3, or 4. In the UK Biobank, we found a pathogenic PRKN mutation in 1.8% of participants and two mutations in ∼1/7800 participants. Those with one PRKN pathogenic variant were as likely as non-carriers to have Parkinson's disease [odds ratio = 0.91 (0.58-1.38), P-value 0.76] or a parent with Parkinson's disease [odds ratio = 1.12 (0.94-1.31), P-value = 0.19]. Similarly, those in the NIH-PD + AMP + PD cohort with one PRKN pathogenic variant were as likely as non-carriers to have Parkinson's disease [odds ratio = 1.29 (0.74-2.38), P-value = 0.43]. Together our results demonstrate that heterozygous pathogenic PRKN mutations are common in the population but do not increase the risk of Parkinson's disease. [ABSTRACT FROM AUTHOR]
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- 2022
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38. RNA binding activity of the recessive parkinsonism protein D J-1 supports involvement in multiple cellular pathways
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van der Brug, Marcel P., Blackinton, Jeff, Chandran, Jayanth, Hao, Ling-Yang, Lal, Ashish, Mazan-Mamczarz, Krystyna, Martindale, Jennifer, Xie, Chengsong, Ahmad, Rili, Thomas, Kelly J.Beilina, Alexandra, Gibbs, J. Raphael, Ding, Jinhui, Myers, Amanda J., Zhan, Ming, Cai, Huaibin, Bonini, Nancy M., Gorospe, Myriam, and Cookson, Mark R.
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Ligand binding (Biochemistry) -- Observations ,Parkinson's disease -- Development and progression ,Parkinson's disease -- Genetic aspects ,Genetic translation -- Research ,Oxidative stress -- Influence ,Neurogenetics -- Research ,Science and technology - Abstract
Parkinson's disease (PD) is a major neurodegenerative condition with several rare Mendelian forms. Oxidative stress and mitochondrial function have been implicated in the pathogenesis of PD but the molecular mechanisms involved in the degeneration of neurons remain unclear. D J-1 mutations are one cause of recessive parkinsonism, but this gene is also reported to be involved in cancer by promoting Ras signaling and suppressing PTEN-induced apoptosis. The specific function of D J-1 is unknown, although it is responsive to oxidative stress and may play a role in the maintenance of mitochondria. Here, we show, using four independent methods, that D J-1 associates with RNA targets in cells and the brain, including mitochondrial genes, genes involved in glutathione metabolism, and members of the PTEN/PI3K cascade. Pathogenic recessive mutants are deficient in this activity. We show that D J-1 is sufficient for RNA binding at nanomolar concentrations. Further, we show that D J-1 binds RNA but dissociates after oxidative stress. These data implicate a single mechanism for the pleiotropic effects of D J-1 in different model systems, namely that the protein binds multiple RNA targets in an oxidation-dependent manner. gene expression | oxidative stress | Parkinson's disease | translation
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- 2008
39. Genotype, haplotype and copy-number variation in worldwide human populations
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Jakobsson, Mattias, Scholz, Sonja W., Scheet, Paul, Gibbs, J. Raphael, VanLiere, Jenna M., Fung, Hon-Chung, Szpiech, Zachary A., Degnan, James H., Wang, Kai, Guerreiro, Rita, Bras, Jose M., Schymick, Jennifer C., Hernandez, Dena G., Traynor, Bryan J., Simon-Sanchez, Javier, Matarin, Mar, Britton, Angela, van de Leemput, Joyce, Rafferty, Ian, Bucan, Maja, Cann, Howard M., Hardy, John A., Rosenberg, Noah A., and Singleton, Andrew B.
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Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
Genome-wide patterns of variation across individuals provide a powerful source of data for uncovering the history of migration, range expansion, and adaptation of the human species. However, high-resolution surveys of [...]
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- 2008
40. Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into the complex genetic architecture
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Chia, Ruth, Sabir, Marya S., Bandres-Ciga, Sara, Saez-Atienzar, Sara, Reynolds, Regina H., Gustavsson, Emil, Walton, Ronald L., Ahmed, Sarah, Viollet, Coralie, Ding, Jinhui, Makarious, Mary B., Diez-Fairen, Monica, Portley, Makayla K., Shah, Zalak, Abramzon, Yevgeniya, Hernandez, Dena G., Blauwendraat, Cornelis, Stone, David J., Eicher, John, Parkkinen, Laura, Ansorge, Olaf, Clark, Lorraine, Honig, Lawrence S., Marder, Karen, Lemstra, Afina, George-Hyslop, Peter St, Londos, Elisabet, Morgan, Kevin, Lashley, Tammaryn, Warner, Thomas T., Jaunmuktane, Zane, Galasko, Douglas, Santana, Isabel, Tienari, Pentti J., Myllykangas, Liisa, Oinas, Minna, Cairns, Nigel J., Morris, John C., Halliday, Glenda M., Van Deerlin, Vivianna M., Trojanowski, John Q., Grassano, Maurizio, Calvo, Andrea, Mora, Gabriele, Canosa, Antonio, Floris, Gianluca, Bohannan, Ryan C., Brett, Francesca, Gan-Or, Ziv, Geiger, Joshua T., Moore, Anni, May, Patrick, Krüger, Rejko, Goldstein, David, Lopez, Grisel, Tayebi, Nahid, Sidransky, Ellen, Palma, Jose-Alberto, Kaufmann, Horacio, Shakkottai, Vikram, Perkins, Matthew, Newell, Kathy L., Gasser, Thomas, Schulte, Claudia, Landi, Francesco, Salvi, Erika, Cusi, Daniele, Masliah, Eliezer, Kim, Ronald C., Caraway, Chad A., Monuki, Ed, Brunetti, Maura, Dawson, Ted M., Rosenthal, Liana S., Albert, Marilyn S., Pletnikova, Olga, Troncoso, Juan C., Flanagan, Margaret E., Mao, Qinwen, Bigio, Eileen H., Rodríguez-Rodríguez, Eloy, Infante, Jon, Lage, Carmen, González-Aramburu, Isabel, Sanchez-Juan, Pascual, Ghetti, Bernardino, Keith, Julia, Black, Sandra E., Masellis, Mario, Rogaeva, Ekaterina, Duyckaerts, Charles, Brice, Alexis, Lesage, Suzanne, Xiromerisiou, Georgia, Barrett, Matthew J., Tilley, Bension S., Gentleman, Steve, Logroscino, Giancarlo, Serrano, Geidy E., Beach, Thomas G., McKeith, Ian G., Thomas, Alan J., Attems, Johannes, Morris, Christopher M., Palmer, Laura, Love, Seth, Troakes, Claire, Al-Sarraj, Safa, Hodges, Angela K., Aarsland, Dag, Klein, Gregory, Kaiser, Scott M., Woltjer, Randy, Pastor, Pau, Bekris, Lynn M., Leverenz, James, Besser, Lilah M., Kuzma, Amanda, Renton, Alan E., Goate, Alison, Bennett, David A., Scherzer, Clemens R., Morris, Huw R., Ferrari, Raffaele, Albani, Diego, Brown, Stuart Pickering, Faber, Kelley, Kukull, Walter, Morenas-Rodriguez, Estrella, Lleó, Alberto, Fortea, Juan, Alcolea, Daniel, Clarimon, Jordi, Nalls, Michael A., Ferrucci, Luigi, Resnick, Susan M., Tanaka, Toshiko, Foroud, Tatiana M., Graff-Radford, Neill R., Wszolek, Zbigniew K., Ferman, Tanis, Boeve, Bradley F., Hardy, John A., Topol, Eric, Torkamani, Ali, Singleton, Andrew B., Ryten, Mina, Dickson, Dennis, Chiò, Adriano, Ross, Owen A., Gibbs, J. Raphael, Dalgard, Clifton L., Traynor, Bryan J., and Scholz, Sonja W.
- Subjects
whole-genome sequencing ,GBA ,Lewy body dementia ,Biochemistry, biophysics & molecular biology [F05] [Life sciences] ,Biochimie, biophysique & biologie moléculaire [F05] [Sciences du vivant] - Abstract
The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer’s and Parkinson’s disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.Competing Interest StatementThomas G. Beach is a consultant for Prothena, Vivid Genomics and Avid Radiopharmaceuticals. He is a scientific advisory board member for Vivid Genomics. John A. Hardy, Huw R. Morris, Stuart Pickering-Brown, Andrew B. Singleton, and Bryan J. Traynor hold US, EU and Canadian patents on the clinical testing and therapeutic intervention for the hexanucleotide repeat expansion of C9orf72. Michael A. Nalls is supported by a consulting contract between Data Tecnica International and the National Institute on Aging, NIH, Bethesda, MD, USA; as a possible conflict of interest Dr. Nalls also consults for Neuron23 Inc., Lysosomal Therapeutics Inc., Illumina Inc., the Michael J. Fox Foundation and Vivid Genomics among others. Jose A. Palma is an editorial board member of Movement Disorders, Parkinsonism & Related Disorders, BMC Neurology, and Clinical Autonomic Research. Bradley F. Boeve, James Leverenz, and Sonja W. Scholz serve on the Scientific Advisory Council of the Lewy Body Dementia Association. Sonja W. Scholz is an editorial board member for the Journal of Parkinson's Disease. Bryan J. Traynor is an editorial board member for JAMA Neurology; Journal of Neurology, Neurosurgery, and Psychiatry; Brain; and Neurobiology of Aging. Zbigniew K. Wszolek serves as a principal investigator or co-principal investigator on Abbvie, Inc. (M15-562 and M15-563), Biogen, Inc. (228PD201) grant, and Biohaven Pharmaceuticals, Inc. (BHV4157-206 and BHV3241-301). Zbigniew K. Wszolek serves as the principal investigator of the Mayo Clinic American Parkinson Disease Association (APDA) Information and Referral Center, and as co-principal investigator of the Mayo Clinic APDA Center for Advanced Research. All other authors report no competing interests.
- Published
- 2020
41. A genome-wide genotyping study in patients with ischaemic stroke: initial analysis and data release
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Matarín, Mar, Brown, W Mark, Scholz, Sonja, Simón-Sánchez, Javier, Fung, Hon-Chung, Hernandez, Dena, Gibbs, J Raphael, De Vrieze, Fabienne Wavrant, Crews, Cynthia, Britton, Angela, Langefeld, Carl D, Brott, Thomas G, Brown, Robert D, Jr, Worrall, Bradford B, Frankel, Michael, Silliman, Scott, Case, L Douglas, Singleton, Andrew, Hardy, John A, Rich, Stephen S, and Meschia, James F
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- 2007
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42. Genome-wide genotyping in amyotrophic lateral sclerosis and neurologically normal controls: first stage analysis and public release of data
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Schymick, Jennifer C, Scholz, Sonja W, Fung, Hon-Chung, Britton, Angela, Arepalli, Sampath, Gibbs, J Raphael, Lombardo, Federica, Matarin, Mar, Kasperaviciute, Dalia, Hernandez, Dena G, Crews, Cynthia, Bruijn, Lucie, Rothstein, Jeffrey, Mora, Gabriele, Restagno, Gabriella, Chiò, Adriano, Singleton, Andrew, Hardy, John, and Traynor, Bryan J
- Published
- 2007
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43. Excessive burden of lysosomal storage disorder gene variants in Parkinson's disease
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Robak, Laurie A., Jansen, Iris E., Rooij, Jeroen van, Uitterlinden, André G., Kraaij, Robert, Jankovic, Joseph, Heutink, Peter, Shulman, Joshua M., Nalls, Mike A., Plagnol, Vincent, Hernandez, Dena G., Sharma, Manu, Sheerin, Una Marie, Saad, Mohamad, Simón-Sánchez, Javier, Schulte, Claudia, Lesage, Suzanne, Sveinbjörnsdóttir, Sigurlaug, Arepalli, Sampath, Barker, Roger, Ben, Yoav, Berendse, Henk W., Berg, Daniela, Bhatia, Kailash, de Bie, Rob M.A., Biffi, Alessandro, Bloem, Bas, Bochdanovits, Zoltan, Bonin, Michael, Bras, Jose M., Brockmann, Kathrin, Brooks, Janet, Burn, David J., Majounie, Elisa, Charlesworth, Gavin, Lungu, Codrin, Chen, Honglei, Chinnery, Patrick F., Chong, Sean, Clarke, Carl E., Cookson, Mark R., Cooper, J. Mark, Corvol, Jean Christophe, Counsell, Carl, Damier, Philippe, Dartigues, Jean François, Deloukas, Panos, Deuschl, Günther, Dexter, David T., van Dijk, Karin D., Dillman, Allissa, Durif, Frank, Dürr, Alexandra, Edkins, Sarah, Evans, Jonathan R., Foltynie, Thomas, Dong, Jing, Gardner, Michelle, Gibbs, J. Raphael, Goate, Alison, Gray, Emma, Guerreiro, Rita, Harris, Clare, van Hilten, Jacobus J., Hofman, Albert, Hollenbeck, Albert, Holton, Janice, Hu, Michele, Huang, Xuemei, Wurster, Isabel, Mätzler, Walter, Hudson, Gavin, Hunt, Sarah E., Huttenlocher, Johanna, Illig, Thomas, Jónsson, Pálmi V., Lambert, Jean Charles, Langford, Cordelia, Lees, Andrew, Lichtner, Peter, Limousin, Patricia, Lopez, Grisel, Lorenz, Delia, McNeill, Alisdair, Moorby, Catriona, Moore, Matthew, Morris, Huw R., Morrison, Karen E., Escott-Price, Valentina, Mudanohwo, Ese, O’sullivan, Sean S., Pearson, Justin, Perlmutter, Joel S., Pétursson, Hjörvar, Pollak, Pierre, Post, Bart, Potter, Simon, Ravina, Bernard, Revesz, Tamas, Riess, Olaf, Rivadeneira, Fernando, Rizzu, Patrizia, Ryten, Mina, Sawcer, Stephen, Schapira, Anthony, Scheffer, Hans, Shaw, Karen, Shoulson, Ira, Shulman, Joshua, Sidransky, Ellen, Smith, Colin, Spencer, Chris C.A., Stefánsson, Hreinn, Bettella, Francesco, Stockton, Joanna D., Strange, Amy, Talbot, Kevin, Tanner, Carlie M., Tashakkori-Ghanbaria, Avazeh, Tison, François, Trabzuni, Daniah, Traynor, Bryan J., Velseboer, Daan, Vidailhet, Marie, Walker, Robert, Warrenburg, Bart van de, Wickremaratchi, Mirdhu, Williams, Nigel, Williams-Gray, Caroline H., Winder-Rhodes, Sophie, Stefánsson, Kári, Martinez, Maria, Wood, Nicholas W., Hardy, John, Brice, Alexis, Gasser, Thomas, Singleton, Andrew B., Erasmus University Medical Center [Rotterdam] (Erasmus MC), Ctr Life Sci Technol, Div Gen Technol, Tsurumi Ku, RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Neurology, ANS - Neurodegeneration, ANS - Amsterdam Neuroscience, Intensive Care Medicine, ANS - Neuroinfection & -inflammation, Graduate School, ACS - Amsterdam Cardiovascular Sciences, APH - Aging & Later Life, Amsterdam Neuroscience - Neurodegeneration, Human genetics, Internal Medicine, and Erasmus MC other
- Subjects
Male ,0301 basic medicine ,Parkinson's disease ,Acid Ceramidase ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Organic Anion Transporters ,ASAH1 protein, human ,Disease ,CTSD protein, human ,Cathepsin D ,genetics [Glucosylceramidase] ,whole exome sequencing ,Cohort Studies ,0302 clinical medicine ,genetics [Parkinson Disease] ,Exome ,genetics ,Exome sequencing ,ComputingMilieux_MISCELLANEOUS ,Aged, 80 and over ,Genetics ,Symporters ,[SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior ,[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences ,genetics [Organic Anion Transporters] ,Middle Aged ,genetics [Lysosomal Storage Diseases] ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,Control subjects ,sphingomyelin phosphodiesterase 1, human ,3. Good health ,sialic acid transport proteins ,Sphingomyelin Phosphodiesterase ,ASAH1 ,Glucosylceramidase ,Female ,Adult ,Genotype ,Biology ,lysosomal storage disorders ,03 medical and health sciences ,medicine ,Humans ,Genetic Predisposition to Disease ,ddc:610 ,Genotyping ,Gene ,Aged ,[SCCO.NEUR]Cognitive science/Neuroscience ,Original Articles ,medicine.disease ,genetics [Symporters] ,genetics [Acid Ceramidase] ,nervous system diseases ,genetics [Cathepsin D] ,030104 developmental biology ,Case-Control Studies ,Mutation ,genetics [Sphingomyelin Phosphodiesterase] ,Neurology (clinical) ,Glucocerebrosidase ,030217 neurology & neurosurgery - Abstract
Item does not contain fulltext Mutations in the glucocerebrosidase gene (GBA), which cause Gaucher disease, are also potent risk factors for Parkinson's disease. We examined whether a genetic burden of variants in other lysosomal storage disorder genes is more broadly associated with Parkinson's disease susceptibility. The sequence kernel association test was used to interrogate variant burden among 54 lysosomal storage disorder genes, leveraging whole exome sequencing data from 1156 Parkinson's disease cases and 1679 control subjects. We discovered a significant burden of rare, likely damaging lysosomal storage disorder gene variants in association with Parkinson's disease risk. The association signal was robust to the exclusion of GBA, and consistent results were obtained in two independent replication cohorts, including 436 cases and 169 controls with whole exome sequencing and an additional 6713 cases and 5964 controls with exome-wide genotyping. In secondary analyses designed to highlight the specific genes driving the aggregate signal, we confirmed associations at the GBA and SMPD1 loci and newly implicate CTSD, SLC17A5, and ASAH1 as candidate Parkinson's disease susceptibility genes. In our discovery cohort, the majority of Parkinson's disease cases (56%) have at least one putative damaging variant in a lysosomal storage disorder gene, and 21% carry multiple alleles. Our results highlight several promising new susceptibility loci and reinforce the importance of lysosomal mechanisms in Parkinson's disease pathogenesis. We suggest that multiple genetic hits may act in combination to degrade lysosomal function, enhancing Parkinson's disease susceptibility.
- Published
- 2017
44. Using genome-wide complex trait analysis to quantify ‘missing heritability’ in Parkinsonʼs disease
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Keller, Margaux F., Saad, Mohamad, Bras, Jose, Bettella, Francesco, Nicolaou, Nayia, Simón-Sánchez, Javier, Mittag, Florian, Büchel, Finja, Sharma, Manu, Gibbs, J. Raphael, Schulte, Claudia, Moskvina, Valentina, Durr, Alexandra, Holmans, Peter, Kilarski, Laura L., Guerreiro, Rita, Hernandez, Dena G., Brice, Alexis, Ylikotila, Pauli, Stefánsson, Hreinn, Majamaa, Kari, Morris, Huw R., Williams, Nigel, Gasser, Thomas, Heutink, Peter, Wood, Nicholas W., Hardy, John, Martinez, Maria, Singleton, Andrew B., and Nalls, Michael A.
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- 2012
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45. Genome-wide genotyping in Parkinson's disease and neurologically normal controls: first stage analysis and public release of data
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Fung, Hon-Chung, Scholz, Sonja, Matarin, Mar, Simón-Sánchez, Javier, Hernandez, Dena, Britton, Angela, Gibbs, J Raphael, Langefeld, Carl, Stiegert, Matt L, Schymick, Jennifer, Okun, Michael S, Mandel, Ronald J, Fernandez, Hubert H, Foote, Kelly D, Rodríguez, Ramón L, Peckham, Elizabeth, De Vrieze, Fabienne Wavrant, Gwinn-Hardy, Katrina, Hardy, John A, and Singleton, Andrew
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- 2006
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46. MAPT expression and splicing is differentially regulated by brain region: relation to genotype and implication for tauopathies
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Trabzuni, Daniah, Wray, Selina, Vandrovcova, Jana, Ramasamy, Adaikalavan, Walker, Robert, Smith, Colin, Luk, Connie, Gibbs, J. Raphael, Dillman, Allissa, Hernandez, Dena G., Arepalli, Sampath, Singleton, Andrew B., Cookson, Mark R., Pittman, Alan M., de Silva, Rohan, Weale, Michael E., Hardy, John, and Ryten, Mina
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- 2012
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47. Exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease
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Johnson, Janel O., Gibbs, J. Raphael, Megarbane, Andre, Urtizberea, J. Andoni, Hernandez, Dena G., Foley, A. Reghan, Arepalli, Sampath, Pandraud, Amelie, Simón-Sánchez, Javier, Clayton, Peter, Reilly, Mary M., Muntoni, Francesco, Abramzon, Yevgeniya, Houlden, Henry, and Singleton, Andrew B.
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- 2012
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48. Missense variant in TREML2 protects against Alzheimer's disease
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Benitez, Bruno A., Jin, Sheng Chih, Guerreiro, Rita, Graham, Rob, Lord, Jenny, Harold, Denise, Sims, Rebecca, Lambert, Jean-Charles, Gibbs, J. Raphael, Bras, Jose, Sassi, Celeste, Harari, Oscar, Bertelsen, Sarah, Lupton, Michelle K., Powell, John, Bellenguez, Celine, Brown, Kristelle, Medway, Christopher, Haddick, Patrick CG., van der Brug, Marcel P., Bhangale, Tushar, Ortmann, Ward, Behrens, Tim, Mayeux, Richard, Pericak-Vance, Margaret A., Farrer, Lindsay A., Schellenberg, Gerard D., Haines, Jonathan L., Turton, Jim, Braae, Anne, Barber, Imelda, Fagan, Anne M., Holtzman, David M., Morris, John C., Williams, Julie, Kauwe, John S.K., Amouyel, Philippe, Morgan, Kevin, Singleton, Andy, Hardy, John, Goate, Alison M., and Cruchaga, Carlos
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- 2014
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49. Allelic heterogeneity and more detailed analyses of known loci explain additional phenotypic variation and reveal complex patterns of association
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Wood, Andrew R., Hernandez, Dena G., Nalls, Michael A., Yaghootkar, Hanieh, Gibbs, J. Raphael, Harries, Lorna W., Chong, Sean, Moore, Matthew, Weedon, Michael N., Guralnik, Jack M., Bandinelli, Stefania, Murray, Anna, Ferrucci, Luigi, Singleton, Andrew B, Melzer, David, and Frayling, Timothy M.
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- 2011
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50. Distinct DNA methylation changes highly correlated with chronological age in the human brain
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Hernandez, Dena G., Nalls, Michael A., Gibbs, J. Raphael, Arepalli, Sampath, van der Brug, Marcel, Chong, Sean, Moore, Matthew, Longo, Dan L., Cookson, Mark R., Traynor, Bryan J., and Singleton, Andrew B.
- Published
- 2011
- Full Text
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